{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:13:30Z","timestamp":1792790010257,"version":"4.5.0"},"reference-count":243,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UKRI-BBSRC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access.<\/jats:p>","DOI":"10.3390\/vaccines12101179","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T04:42:15Z","timestamp":1729140135000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-2434","authenticated-orcid":false,"given":"Andrea","family":"Lafleur","sequence":"first","affiliation":[{"name":"Doctoral Training Centre, University of Oxford, Oxford OX1 3NP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-3670","authenticated-orcid":false,"given":"Stephane","family":"Daffis","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-8116","authenticated-orcid":false,"given":"Charles","family":"Mowbray","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Arana","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), 1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(07)70209-8","article-title":"Cutaneous leishmaniasis","volume":"7","author":"Reithinger","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1529-8019.2009.01272.x","article-title":"Cutaneous and mucocutaneous leishmaniasis","volume":"22","author":"David","year":"2009","journal-title":"Dermatol. Ther."},{"key":"ref_4","unstructured":"World Health Organization (2023, January 12). Leishmaniasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_5","unstructured":"World Health Organization, and Alvar, J. (2008). Report of the Consultative Meeting on Cutaneous leishmaniasis, World Health Organization. Available online: https:\/\/www.who.int\/publications-detail-redirect\/WHO-HTM-NTD-IDM-2008.7."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1515\/jtim-2015-0002","article-title":"Leishmaniasis revisited: Current aspects on epidemiology, diagnosis and treatment","volume":"3","author":"Georgiadou","year":"2015","journal-title":"J. Transl. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., and den Boer, M. (2012). Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1001\/jamadermatol.2018.2133","article-title":"Incidence of Endemic Human Cutaneous Leishmaniasis in the United States","volume":"154","author":"McIlwee","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_9","unstructured":"Pan American Health Organization WHO (2018). Leishmaniasis in the Americas. Recommendations for the Treatment, Pan American Health Organization. Available online: https:\/\/www.paho.org\/en\/documents\/leishmaniasis-americas-recommendations-treatment-2018."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1086\/503371","article-title":"Resistance to Antimony and Treatment Failure in Human Leishmania (Viannia) Infection","volume":"193","author":"Rojas","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_11","unstructured":"(2023, December 13). Control of the Leishmaniases WHO TRS n\u00b0 949. Available online: https:\/\/www.who.int\/publications-detail-redirect\/WHO-TRS-949."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aruleba, R.T., Carter, K.C., Brombacher, F., and Hurdayal, R. (2020). Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?. Microorganisms, 8.","DOI":"10.3390\/microorganisms8071069"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Scorza, B.M., Carvalho, E.M., and Wilson, M.E. (2017). Cutaneous Manifestations of Human and Murine Leishmaniasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061296"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3347\/kjp.2008.46.3.191","article-title":"Distribution Frequency of Pathogenic Bacteria Isolated from Cutaneus Leishmaniasis Lesions","volume":"46","author":"Ziaei","year":"2008","journal-title":"Korean J. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-3024.2009.01116.x","article-title":"Immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis in American cutaneous leishmaniasis","volume":"31","author":"Silveira","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Volpedo, G., Pacheco-Fernandez, T., Holcomb, E.A., Cipriano, N., Cox, B., and Satoskar, A.R. (2021). Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis and Post Kala-azar Dermal Leishmaniasis (PKDL). Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.685296"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cellimm.2016.07.013","article-title":"Leishmania exosomes and other virulence factors: Impact on innate immune response and macrophage functions","volume":"309","author":"Atayde","year":"2016","journal-title":"Cell. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri.2016.72","article-title":"Cutaneous leishmaniasis: Immune responses in protection and pathogenesis","volume":"16","author":"Scott","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tomiotto-Pellissier, F., Bortoleti, B.T.d.S., Assolini, J.P., Gon\u00e7alves, M.D., Carloto, A.C.M., Miranda-Sapla, M.M., Conchon-Costa, I., Bordignon, J., and Pavanelli, W.R. (2018). Macrophage Polarization in Leishmaniasis: Broadening Horizons. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02529"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.coi.2020.08.004","article-title":"Leishmania Viannia guyanensis, LRV1 virus and extracellular vesicles: A dangerous trio influencing the faith of immune response during muco-cutaneous leishmaniasis","volume":"66","author":"Olivier","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/20477724.2016.1232042","article-title":"Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: A review","volume":"110","author":"Maspi","year":"2016","journal-title":"Pathog. Glob. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.4049\/jimmunol.180.6.4090","article-title":"IL-10 and TGF-\u03b2 Control the Establishment of Persistent and Transmissible Infections Produced by Leishmania tropica in C57BL\/6 Mice","volume":"180","author":"Anderson","year":"2008","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.4110\/in.2024.24.e14","article-title":"Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms","volume":"24","author":"Becker","year":"2024","journal-title":"Immune Netw."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"753","DOI":"10.4269\/ajtmh.17-0624","article-title":"Regulatory T-Cell Dynamics in Cutaneous and Mucocutaneous Leishmaniasis due to Leishmania braziliensis","volume":"98","author":"Barros","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.3201\/eid1309.061446","article-title":"Recurrent American Cutaneous Leishmaniasis","volume":"13","author":"Gangneux","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1086\/322643","article-title":"Leishmaniasis Recidivans Recurrence after 43 Years: A Clinical and Immunologic Report after Successful Treatment","volume":"33","author":"Marovich","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1086\/313924","article-title":"Cutaneous Leishmaniasis following Local Trauma: A Clinical Pearl","volume":"31","author":"Wortmann","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3855\/jidc.8516","article-title":"Leishmaniasis recidivans in Ethiopia: Cutaneous and mucocutaneous features","volume":"11","author":"Dassoni","year":"2017","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1365-4632.2004.02518.x","article-title":"Leishmaniasis recidiva cutis due to Leishmania (Viannia) panamensis in subtropical Ecuador: Isoenzymatic characterization","volume":"45","author":"Calvopina","year":"2006","journal-title":"Int. J. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/intimm\/dxr088","article-title":"The CD40\u2013CD40L axis and IFN-\u03b3 play critical roles in Langhans giant cell formation","volume":"24","author":"Sakai","year":"2012","journal-title":"Int. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.immuni.2016.09.014","article-title":"Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection","volume":"45","author":"Cronan","year":"2016","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Morimoto, A., Omachi, S., Osada, Y., Chambers, J.K., Uchida, K., Sanjoba, C., Matsumoto, Y., and Goto, Y. (2016). Hemophagocytosis in Experimental Visceral Leishmaniasis by Leishmania donovani. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004505"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.pt.2019.12.010","article-title":"Iron and Heme Metabolism at the Leishmania-Host Interface","volume":"36","author":"Hamza","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1089\/ten.teb.2017.0242","article-title":"Multinucleated Giant Cells: Good Guys or Bad Guys?","volume":"24","author":"Miron","year":"2018","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1365-4632.2010.04419.x","article-title":"Leishmaniasis recidivans among school children in Bam, South-east Iran, 1994\u20132006","volume":"49","author":"Sharifi","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/trstmh\/trz037","article-title":"What makes mucosal and anergic diffuse cutaneous leishmaniases so clinically and immunopathogically different? A review in Brazil","volume":"113","author":"Silveira","year":"2019","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1590\/S0074-02762004000300001","article-title":"Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: A review","volume":"99","author":"Silveira","year":"2004","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1590\/S0001-37652004000300006","article-title":"The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis","volume":"76","author":"Pinheiro","year":"2004","journal-title":"An. Acad. Bras. Ci\u00eanc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e126207","DOI":"10.1172\/jci.insight.126207","article-title":"TLR9\/MyD88\/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection","volume":"4","author":"Sauter","year":"2019","journal-title":"JCI Insight"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nogueira, P.M., Assis, R.R., Torrecilhas, A.C., Saraiva, E.M., Pessoa, N.L., Campos, M.A., Marialva, E.F., R\u00edos-Velasquez, C.M., Pessoa, F.A., and Secundino, N.F. (2016). Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory Properties via TLR4 and Do Not Affect Sand Fly Infection. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004848"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ca\u00f1eda-Guzm\u00e1n, I.C., Salaiza-Suazo, N., Fern\u00e1ndez-Figueroa, E.A., Carrada-Figueroa, G., Aguirre-Garc\u00eda, M., and Becker, I. (2014). NK Cell Activity Differs between Patients with Localized and Diffuse Cutaneous Leishmaniasis Infected with Leishmania mexicana: A Comparative Study of TLRs and Cytokines. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112410"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.4269\/ajtmh.2006.75.1074","article-title":"Relapse of New World Diffuse Cutaneous Leishmaniasis Caused By Leishmania (Leishmania) Mexicana after Miltefosine Treatment","volume":"75","author":"Cooper","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1046\/j.1365-3156.1999.00491.x","article-title":"Treatment of two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana modifies the immunohistological profile but not the disease outcome","volume":"4","author":"Volkow","year":"1999","journal-title":"Trop. Med. Int. Health"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1111\/j.1365-2133.2007.07872.x","article-title":"Diffuse cutaneous leishmaniasis responds to miltefosine but then relapses","volume":"156","author":"Zerpa","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1590\/abd1806-4841.20198775","article-title":"Disseminated leishmaniasis: Clinical, pathogenic, and therapeutic aspects","volume":"94","author":"Machado","year":"2019","journal-title":"An. Bras. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1086\/345772","article-title":"Disseminated Leishmaniasis: A New and Emerging Form of Leishmaniasis Observed in Northeastern Brazil","volume":"186","author":"Turetz","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.trstmh.2011.05.002","article-title":"Reappraisal of the immunopathogenesis of disseminated leishmaniasis: In Situ and systemic immune response","volume":"105","author":"Machado","year":"2011","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1590\/S0074-02762013000100003","article-title":"Inflammation in disseminated lesions: An analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis","volume":"108","author":"Mendes","year":"2013","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/pim.12007","article-title":"Tissue damage and immunity in cutaneous leishmaniasis","volume":"34","author":"Eidsmo","year":"2012","journal-title":"Parasite Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00281-012-0350-8","article-title":"Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis","volume":"34","author":"Soong","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/1469-0691.12095","article-title":"The therapeutic potential of immune cross-talk in leishmaniasis","volume":"19","author":"Hartley","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1365-3024.2009.01125.x","article-title":"Recruitment of CD8+ T cells expressing granzymeA is associated with lesion progression in human cutaneous leishmaniasis","volume":"31","author":"Faria","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Crosby, E.J., Goldschmidt, M.H., Wherry, E.J., and Scott, P. (2014). Engagement of NKG2D on Bystander Memory CD8 T Cells Promotes Increased Immunopathology following Leishmania major Infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003970"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1002\/eji.200940115","article-title":"Human mucosal leishmaniasis: Neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines","volume":"40","author":"Boaventura","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hartley, M.-A., Bourreau, E., Rossi, M., Castiglioni, P., Eren, R.O., Prevel, F., Couppi\u00e9, P., Hickerson, S.M., Launois, P., and Beverley, S.M. (2016). Leishmaniavirus-Dependent Metastatic Leishmaniasis Is Prevented by Blocking IL-17A. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005852"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1128\/IAI.00959-09","article-title":"CXCL10 Production by Human Monocytes in Response to Leishmania braziliensis Infection","volume":"78","author":"Hogg","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Carvalho, J.d.P., Silva, S.N., Freire, M.L., Alves, L.L., de Souza, C.S.A., and Cota, G. (2022). The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010931"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"547","DOI":"10.4161\/viru.2.6.17839","article-title":"Muco-cutaneous leishmaniasis in the New World","volume":"2","author":"Ronet","year":"2011","journal-title":"Virulence"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Strazzulla, A., Cocuzza, S., Pinzone, M.R., Postorino, M.C., Cosentino, S., Serra, A., Cacopardo, B., and Nunnari, G. (2013). Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/805108"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trstmh.2003.08.001","article-title":"Risk factors for mucosal manifestation of American cutaneous leishmaniasis","volume":"99","author":"Caiaffa","year":"2005","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1128\/IAI.72.1.508-514.2004","article-title":"Multiclonal Leishmania braziliensis Population Structure and Its Clinical Implication in a Region of Endemicity for American Tegumentary Leishmaniasis","volume":"72","author":"Schriefer","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"871","DOI":"10.3201\/eid1506.080406","article-title":"Geographic Clustering of Leishmaniasis in Northeastern Brazil1","volume":"15","author":"Schriefer","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1128\/JCM.02064-12","article-title":"Association between an Emerging Disseminated form of Leishmaniasis and Leishmania (Viannia) braziliensis Strain Polymorphisms","volume":"50","author":"Queiroz","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/infdis\/jiv355","article-title":"Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse","volume":"213","author":"Bourreau","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/infdis\/jiv354","article-title":"Association of the Endobiont Double-Stranded RNA Virus LRV1 with Treatment Failure for Human Leishmaniasis Caused by Leishmania braziliensis in Peru and Bolivia","volume":"213","author":"Adaui","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1126\/science.1199326","article-title":"Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis","volume":"331","author":"Ives","year":"2011","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4987","DOI":"10.1073\/pnas.1621447114","article-title":"Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis","volume":"114","author":"Rossi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102004","DOI":"10.1016\/j.isci.2020.102004","article-title":"Endosymbiotic RNA virus inhibits Leishmania-induced caspase-11 activation","volume":"24","author":"Zamboni","year":"2021","journal-title":"iScience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"137","DOI":"10.15698\/mic2018.03.619","article-title":"Leishmania guyanensis parasites block the activation of the inflammasome by inhibiting maturation of IL-1\u03b2","volume":"5","author":"Hartley","year":"2018","journal-title":"Microb. Cell Graz Austria"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5273","DOI":"10.1038\/s41467-019-13356-2","article-title":"Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition","volume":"10","author":"Dilucca","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/cei.12787","article-title":"Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India","volume":"185","author":"Kaushal","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kumar, A., Singh, V.K., Tiwari, R., Madhukar, P., Kumar, S., Gautam, V., Engwerda, C., Sundar, S., and Kumar, R. (2023). Post kala-azar dermal leishmaniasis in the Indian sub-continent: Challenges and strategies for elimination. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1236952"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1016\/S0035-9203(01)90219-6","article-title":"Leishmaniasis in Sudan. Post kala-azar dermal leishmaniasis","volume":"95","author":"Zijlstra","year":"2001","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0035-9203(01)90110-5","article-title":"Ethiopian visceral leishmaniasis: Generic and proprietary sodium stibogluconate are equivalent; HIV co-infected patients have a poor outcome","volume":"95","author":"Ritmeijer","year":"2001","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mondal, S., Bhattacharya, P., Rahaman, M., Ali, N., and Goswami, R.P. (2010). A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000764"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Katara, G.K., Ansari, N.A., Verma, S., Ramesh, V., and Salotra, P. (2011). Foxp3 and IL-10 Expression Correlates with Parasite Burden in Lesional Tissues of Post Kala Azar Dermal Leishmaniasis (PKDL) Patients. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001171"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/(SICI)1096-9896(199912)189:4<615::AID-PATH466>3.0.CO;2-Z","article-title":"Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile","volume":"189","author":"Ismail","year":"1999","journal-title":"J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1046\/j.1365-2249.2000.01163.x","article-title":"The development of post-kala-azar dermal leishmaniasis (PKDL) is associated with acquisition of Leishmania reactivity by peripheral blood mononuclear cells (PBMC)","volume":"119","author":"Gasim","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Katara, G.K., Ansari, N.A., Singh, A., Ramesh, V., and Salotra, P. (2012). Evidence for Involvement of Th17 Type Responses in Post Kala Azar Dermal Leishmaniasis (PKDL). PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001703"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ijpddr.2019.08.005","article-title":"In-situ immune profile of polymorphic vs. macular Indian Post Kala-azar dermal leishmaniasis","volume":"11","author":"Sengupta","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mukherjee, S., Sengupta, R., Mukhopadhyay, D., Braun, C., Mitra, S., Roy, S., Kanti Das, N., Chatterjee, U., von Stebut, E., and Chatterjee, M. (2019). Impaired activation of lesional CD8+ T-cells is associated with enhanced expression of Programmed Death-1 in Indian Post Kala-azar Dermal Leishmaniasis. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37144-y"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mukhopadhyay, D., Mukherjee, S., Roy, S., Dalton, J.E., Kundu, S., Sarkar, A., Das, N.K., Kaye, P.M., and Chatterjee, M. (2015). M2 Polarization of Monocytes-Macrophages Is a Hallmark of Indian Post Kala-Azar Dermal Leishmaniasis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004145"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4103\/ijd.IJD_264_20","article-title":"Therapeutic Modalities in Post Kala-azar Dermal Leishmaniasis: A Systematic Review of the Effectiveness and Safety of the Treatment Options","volume":"66","author":"Datta","year":"2021","journal-title":"Indian J. Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"155248","DOI":"10.1016\/j.cyto.2020.155248","article-title":"The different faces of the NLRP3 inflammasome in cutaneous Leishmaniasis: A review","volume":"147","author":"Kihel","year":"2021","journal-title":"Cytokine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/00000372-200208000-00006","article-title":"Interferon-\u03b3 Treatment Induces Granulomatous Tissue Reaction in a Case of Localized Cutaneous Leishmaniasis","volume":"24","author":"Haas","year":"2002","journal-title":"Am. J. Dermatopathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1084\/jem.20030159","article-title":"Interleukin 1\u03b1 Promotes Th1 Differentiation and Inhibits Disease Progression in Leishmania major\u2013susceptible BALB\/c Mice","volume":"198","author":"Ehrchen","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/sj.jid.5700309","article-title":"Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections","volume":"126","author":"Kostka","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1002\/1521-4141(200211)32:11<3206::AID-IMMU3206>3.0.CO;2-J","article-title":"Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent","volume":"32","author":"Buxbaum","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1128\/IAI.68.5.2449-2456.2000","article-title":"Potentiality of Interleukin-18 as a Useful Reagent for Treatment and Prevention of Leishmania major Infection","volume":"68","author":"Ohkusu","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e12805","DOI":"10.1111\/pim.12805","article-title":"CXCL10 immunomodulatory effect against infection caused by an antimony refractory isolate of Leishmania braziliensis in mice","volume":"43","author":"Dutra","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12461","DOI":"10.1111\/pim.12461","article-title":"Leishmania tarentolae expressing CXCL-10 as an efficient immunotherapy approach against Leishmania major-infected BALB\/c mice","volume":"39","author":"Abdossamadi","year":"2017","journal-title":"Parasite Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1086\/320699","article-title":"Combined Interleukin-12 and Topical Chemotherapy for Established Leishmaniasis Drastically Reduces Tissue Parasitism and Relapses in Susceptible Mice","volume":"183","author":"Fernandes","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5715","DOI":"10.1128\/IAI.70.10.5715-5720.2002","article-title":"Combined Treatment with Interleukin-12 and Indomethacin Promotes Increased Resistance in BALB\/c Mice with Established Leishmania major Infections","volume":"70","author":"Li","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1086\/424848","article-title":"Antimony plus recombinant human granulocyte-macrophage colony-stimulating factor applied topically in low doses enhances healing of cutaneous Leishmaniasis ulcers: A randomized, double-blind, placebo-controlled study","volume":"190","author":"Santos","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1086\/315082","article-title":"Randomized, Double-Blind Study of Stibogluconate Plus Human Granulocyte Macrophage Colony-Stimulating Factor versus Stibogluconate Alone in the Treatment of Cutaneous Leishmaniasis","volume":"180","author":"Almeida","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ijid.2020.11.183","article-title":"Association of miltefosine with granulocyte and macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis in the Amazon region: A randomized and controlled trial","volume":"103","author":"Mendes","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e2465","DOI":"10.1093\/cid\/ciaa1337","article-title":"A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil","volume":"73","author":"Machado","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e2789859","DOI":"10.1155\/2020\/2789859","article-title":"Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis","volume":"2020","author":"Peixoto","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1128\/iai.65.8.3225-3230.1997","article-title":"Successful therapy of chronic, nonhealing murine cutaneous leishmaniasis with sodium stibogluconate and gamma interferon depends on continued interleukin-12 production","volume":"65","author":"Li","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_100","first-page":"1125","article-title":"Topical application of human fibroblast interferon (IFN) in cutaneous leishmaniasis","volume":"23","author":"Trau","year":"1987","journal-title":"Isr. J. Med. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1749-6632.2009.05069.x","article-title":"Clinical Use of Interferon-\u03b3","volume":"1182","author":"Miller","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"896","DOI":"10.4049\/jimmunol.165.2.896","article-title":"IL-12 Is Required to Maintain a Th1 Response During Leishmania major Infection1","volume":"165","author":"Park","year":"2000","journal-title":"J. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ymeth.2013.04.010","article-title":"Quantitative analysis of global phosphorylation changes with high-resolution tandem mass spectrometry and stable isotopic labeling","volume":"61","author":"Kweon","year":"2013","journal-title":"Methods"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.4049\/jimmunol.154.9.4623","article-title":"IL-12 enhances Th1-type responses in human Leishmania donovani infections","volume":"154","author":"Ghalib","year":"1995","journal-title":"J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.cyto.2015.01.021","article-title":"IL-18 contributes to susceptibility to Leishmania amazonensis infection by macrophage-independent mechanisms","volume":"74","author":"Sousa","year":"2015","journal-title":"Cytokine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4269\/ajtmh.2005.73.79","article-title":"Successful Treatment of Refractory Cutaneous Leishmaniasis with Gm-Csf and Antimonials","volume":"73","author":"Almeida","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1365-3083.2007.02025.x","article-title":"Induction of Host Protective Th1 Immune Response by Chemokines in Leishmania donovani-infected BALB\/c Mice","volume":"66","author":"Dey","year":"2007","journal-title":"Scand. J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1476-5381.2009.00206.x","article-title":"Current status and challenges of cytokine pharmacology","volume":"157","author":"Anzenbacher","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1084\/jem.194.10.1497","article-title":"The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti\u2013IL-10 Receptor Antibody for Sterile Cure","volume":"194","author":"Belkaid","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/IAI.01398-08","article-title":"Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis due to Leishmania guyanensis","volume":"77","author":"Bourreau","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e152741","DOI":"10.1155\/2015\/152741","article-title":"Potential Use of Interleukin-10 Blockade as a Therapeutic Strategy in Human Cutaneous Leishmaniasis","volume":"2015","author":"Castellano","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Novais, F.O., Carvalho, A.M., Clark, M.L., Carvalho, L.P., Beiting, D.P., Brodsky, I.E., Carvalho, E.M., and Scott, P. (2017). CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1\u03b2 production. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006196"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1128\/IAI.73.7.3903-3911.2005","article-title":"Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis","volume":"73","author":"Murray","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cytogfr.2020.06.007","article-title":"IL-1 family and Cutaneous Leishmaniasis: A poorly understood relationship","volume":"57","author":"Amorim","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/intimm\/dxq006","article-title":"IL-1-induced inflammation promotes development of leishmaniasis in susceptible BALB\/c mice","volume":"22","author":"Voronov","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/mabs.2.1.10328","article-title":"Canakinumab","volume":"2","author":"Dhimolea","year":"2010","journal-title":"mAbs"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"de Freitas e Silva, R., and von Stebut, E. (2021). Unraveling the Role of Immune Checkpoints in Leishmaniasis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.620144"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.3389\/fimmu.2017.01492","article-title":"Immune Checkpoint Targets for Host-Directed Therapy to Prevent and Treat Leishmaniasis","volume":"8","author":"Kumar","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0165-2478(03)00137-8","article-title":"Involvement of ICOS-B7RP-1 costimulatory pathway in the regulation of immune responses to Leishmania major and Nippostrongylus brasiliensis infections","volume":"89","author":"Miyahira","year":"2003","journal-title":"Immunol. Lett."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"da Fonseca-Martins, A.M., Ramos, T.D., Pratti, J.E.S., Firmino-Cruz, L., Gomes, D.C.O., Soong, L., Saraiva, E.M., and de Matos Guedes, H.L. (2019). Immunotherapy using anti-PD-1 and anti-PD-L1 in Leishmania amazonensis-infected BALB\/c mice reduce parasite load. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56336-8"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1084\/jem.191.2.375","article-title":"Critical Contribution of Ox40 Ligand to T Helper Cell Type 2 Differentiation in Experimental Leishmaniasis","volume":"191","author":"Akiba","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1128\/IAI.67.12.6454-6460.1999","article-title":"Interleukin-4-Independent Acceleration of Cutaneous Leishmaniasis in Susceptible BALB\/c Mice following Treatment with Anti-CTLA4 Antibody","volume":"67","author":"Heinzel","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.exppara.2014.11.002","article-title":"Ox40L\u2013Ox40 pathway plays distinct roles in regulating Th2 responses but does not determine outcome of cutaneous leishmaniasis caused by Leishmania mexicana and Leishmania major","volume":"148","author":"Tuladhar","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1002\/eji.200324021","article-title":"Immunotherapy with OX40L-Fc or anti-CTLA-4 enhances local tissue responses and killing of Leishmania donovani","volume":"34","author":"Zubairi","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1002\/(SICI)1521-4141(199812)28:12<4213::AID-IMMU4213>3.0.CO;2-C","article-title":"CTLA4 (CD152) modulates the Th subset response and alters the course of experimental Leishmania major infection","volume":"28","author":"Saha","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/infdis\/174.6.1303","article-title":"Blockade of CD86 Ameliorates Leishmania major Infection by Down-Regulating the Th2 Response","volume":"174","author":"Brown","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Faleiro, R.J., Kumar, R., Bunn, P.T., Singh, N., Chauhan, S.B., Sheel, M., Amante, F.H., de Oca, M.M., Edwards, C.L., and Ng, S.S. (2016). Combined Immune Therapy for the Treatment of Visceral Leishmaniasis. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004415"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1128\/AAC.47.8.2513-2517.2003","article-title":"Immunoenhancement Combined with Amphotericin B as Treatment for Experimental Visceral Leishmaniasis","volume":"47","author":"Murray","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"930257","DOI":"10.1155\/2012\/930257","article-title":"Toll-Like Receptors in Leishmania Infections: Guardians or Promoters?","volume":"2012","author":"Faria","year":"2012","journal-title":"J. Parasitol. Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Huang, L., Hinchman, M., and Mendez, S. (2015). Coinjection with TLR2 Agonist Pam3CSK4 Reduces the Pathology of Leishmanization in Mice. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003546"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1093\/jac\/dkm079","article-title":"A trial of immunotherapy against Leishmania amazonensis infection in vitro and in vivo with Z-100, a polysaccharide obtained from Mycobacterium tuberculosis, alone or combined with meglumine antimoniate","volume":"59","author":"Barroso","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4269\/ajtmh.2002.67.184","article-title":"Inhibition of intracellular proliferation of Leishmania parasites in vitro and suppression of skin lesion development in BALB\/c mice by a novel lipid A analog (ONO-4007)","volume":"67","author":"Khan","year":"2002","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1016\/j.vaccine.2006.03.023","article-title":"Efficacy of vaccination with a combination of Leishmania amastigote antigens and the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against Leishmania amazonensis infection in a murine model of New World cutaneous leishmaniasis","volume":"24","author":"Calvopina","year":"2006","journal-title":"Vaccine"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1086\/314782","article-title":"Treatment of Experimental Leishmaniasis with the Immunomodulators Imiquimod and S-28463: Efficacy and Mode of Action","volume":"179","author":"Buates","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_135","first-page":"45","article-title":"Immunotherapy with Imiquimod increases the efficacy of Glucantime therapy of Leishmania major infection","volume":"8","author":"Khalili","year":"2011","journal-title":"Iran. J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1046\/j.1365-4362.2003.01955.x","article-title":"Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod","volume":"42","author":"Seeberger","year":"2003","journal-title":"Int. J. Dermatol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/j.1365-4632.2008.04010.x","article-title":"Tropical medicine rounds: Treatment of Old World cutaneous leishmaniasis with dapsone, itraconazole, cryotherapy, and imiquimod, alone and in combination","volume":"48","author":"Alshiltawy","year":"2009","journal-title":"Int. J. Dermatol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.biomaterials.2016.09.004","article-title":"Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model","volume":"108","author":"Siefert","year":"2016","journal-title":"Biomaterials"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.1128\/IAI.73.8.4948-4954.2005","article-title":"Prevention and treatment of cutaneous leishmaniasis in primates by using synthetic type D\/A oligodeoxynucleotides expressing CpG motifs","volume":"73","author":"Flynn","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.4049\/jimmunol.170.9.4717","article-title":"CpG Oligodeoxynucleotides Protect Normal and SIV-Infected Macaques from Leishmania Infection1","volume":"170","author":"Verthelyi","year":"2003","journal-title":"J. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Thacker, S.G., McWilliams, I.L., Bonnet, B., Halie, L., Beaucage, S., Rachuri, S., Dey, R., Duncan, R., Modabber, F., and Robinson, S. (2020). CpG ODN D35 improves the response to abbreviated low-dose pentavalent antimonial treatment in non-human primate model of cutaneous leishmaniasis. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008050"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"6488","DOI":"10.1093\/nar\/gkl867","article-title":"Use of thermolytic protective groups to prevent G-tetrad formation in CpG ODN type D: Structural studies and immunomodulatory activity in primates","volume":"34","author":"Puig","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1086\/429238","article-title":"Randomized, Double-Blind Clinical Trial of Topical Imiquimod 5% with Parenteral Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis in Peru","volume":"40","author":"Ward","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1086\/324161","article-title":"Successful Treatment of Drug-Resistant Cutaneous Leishmaniasis in Humans by Use of Imiquimod, an Immunomodulator","volume":"33","author":"Arevalo","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1001\/archderm.142.12.1575","article-title":"Imiquimod in Combination with Meglumine Antimoniate for Cutaneous Leishmaniasis: A Randomized Assessor-Blind Controlled Trial","volume":"142","author":"Firooz","year":"2006","journal-title":"Arch. Dermatol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1086\/518172","article-title":"Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis","volume":"44","author":"Arevalo","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Miranda-Verastegui, C., Tulliano, G., Gyorkos, T.W., Calderon, W., Rahme, E., Ward, B., Cruz, M., Llanos-Cuentas, A., and Matlashewski, G. (2009). First-Line Therapy for Human Cutaneous Leishmaniasis in Peru Using the TLR7 Agonist Imiquimod in Combination with Pentavalent Antimony. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000491"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.exppara.2006.12.004","article-title":"Leishmania major: In Vitro and in vivo anti-leishmanial activity of paromomycin ointment (Leshcutan) combined with the immunomodulator Imiquimod","volume":"116","author":"Bazarsky","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e0305-2020","DOI":"10.1590\/0037-8682-0305-2020","article-title":"Efficacy of imiquimod 5% cream as first-line management in cutaneous leishmaniasis caused by Leishmania mexicana","volume":"54","author":"Becker","year":"2021","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41416-022-01876-6","article-title":"Toll-like receptor 9 agonists and combination therapies: Strategies to modulate the tumour immune microenvironment for systemic anti-tumour immunity","volume":"127","author":"Dongye","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"10039","DOI":"10.2147\/OTT.S247050","article-title":"Toll-Like Receptor 9 Agonists in Cancer","volume":"13","author":"Karapetyan","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Montakhab-Yeganeh, H., Shafiei, R., Najm, M., Masoori, L., Aspatwar, A., and Badirzadeh, A. (2022). Immunogenic properties of empty pcDNA3 plasmid against zoonotic cutaneous leishmaniasis in mice. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0263993"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1128\/IAI.71.9.5121-5129.2003","article-title":"Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability","volume":"71","author":"Mendez","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_154","unstructured":"(2023, December 06). CpG-D35 (DNDI-2319)|DNDi. 31 December 2013. Available online: https:\/\/dndi.org\/research-development\/portfolio\/dndi-2319\/."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Schleicher, U., Liese, J., Justies, N., Mischke, T., Haeberlein, S., Sebald, H., Kalinke, U., Weiss, S., and Bogdan, C. (2018). Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control of Leishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or Secondary L. major Infection. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00079"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Carneiro, P.P., D\u00f3rea, A.S., Oliveira, W.N., Guimar\u00e3es, L.H., Brodskyn, C., Carvalho, E.M., and Bacellar, O. (2021). Blockade of TLR2 and TLR4 Attenuates Inflammatory Response and Parasite Load in Cutaneous Leishmaniasis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.706510"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"M\u00fcnck, N.-A., Roth, J., Sunderk\u00f6tter, C., and Ehrchen, J. (2019). Aryl Hydrocarbon Receptor-Signaling Regulates Early Leishmania major-Induced Cytokine Expression. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02442"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1128\/AAC.00617-06","article-title":"Glibenclamide, a Blocker of K+ATP Channels, Shows Antileishmanial Activity in Experimental Murine Cutaneous Leishmaniasis","volume":"50","author":"Payares","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4103\/1687-7942.163415","article-title":"Immunomodulatory role of ATP inhibitor: Glibenclamide and its impact on the pathogenesis of murine Leishmania major infection","volume":"8","year":"2015","journal-title":"Parasitol. United J."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jid.2019.05.025","article-title":"Glyburide, a NLRP3 Inhibitor, Decreases Inflammatory Response and Is a Candidate to Reduce Pathology in Leishmania braziliensis Infection","volume":"140","author":"Carvalho","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/jpnr.JPNR_1_17","article-title":"The evaluation of quercetin and luteolin efficacy on cutaneous leishmaniasis in mice infected with Leishmania major","volume":"8","author":"Hamidizadeh","year":"2017","journal-title":"J. Pharm. Negat. Results"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1055\/s-0028-1088382","article-title":"Oral Metabolism and Efficacy of Kalanchoe pinnata Flavonoids in a Murine Model of Cutaneous Leishmaniasis","volume":"75","author":"Muzitano","year":"2009","journal-title":"Planta Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e1878170","DOI":"10.1155\/2023\/1878170","article-title":"Topically Applied Luteolin \/Quercetin-Capped Silver Nanoparticle Ointment as Antileishmanial Composite: Acceleration Wound Healing in BALB\/c Mice","volume":"2023","author":"Ebrahimzadeh","year":"2023","journal-title":"Adv. Mater. Sci. Eng."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1017\/S003118201700097X","article-title":"Lipid-core nanocapsules increase the oral efficacy of quercetin in cutaneous leishmaniasis","volume":"144","author":"Poletto","year":"2017","journal-title":"Parasitology"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"dos Santos, R.F., Da Silva, T., Brito, A.C.d.S., In\u00e1cio, J.D., Ventura, B.D., Mendes, M.A.P., Azevedo, B.F., Siqueira, L.M., Almeida-Amaral, E.E., and Dutra, P.M.L. (2023). Therapeutic effect of oral quercetin in hamsters infected with Leishmania Viannia braziliensis. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1059168"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.parint.2015.10.007","article-title":"Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection","volume":"65","author":"Hoseini","year":"2016","journal-title":"Parasitol. Int."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ejps.2014.06.010","article-title":"Topical treatment of L. major infected BALB\/c mice with a novel diselenide chitosan hydrogel formulation","volume":"62","author":"Schwartz","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jddst.2018.12.031","article-title":"Combination of amphotericin B and chitosan platelets for the treatment of experimental cutaneous leishmaniasis: Histological and immunohistochemical examinations","volume":"50","author":"Malli","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4103\/ijdvl.IJDVL_189_18","article-title":"Chitosan-based biocompatible dressing for treatment of recalcitrant lesions of cutaneous leishmaniasis: A pilot clinical study","volume":"85","author":"Abdollahimajd","year":"2019","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Abdossamadi, Z., Seyed, N., Zahedifard, F., Taheri, T., Taslimi, Y., Montakhab-Yeganeh, H., Badirzadeh, A., Vasei, M., Gharibzadeh, S., and Rafati, S. (2017). Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB\/c mice. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006123"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2217\/imt-2017-0076","article-title":"Live Leishmania tarentolae secreting HNP1 as an immunotherapeutic tool against Leishmania infection in BALB\/c mice","volume":"9","author":"Abdossamadi","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Riezk, A., Van Bocxlaer, K., Yardley, V., Murdan, S., and Croft, S.L. (2020). Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis. Molecules, 25.","DOI":"10.3390\/molecules25174002"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2217\/nnm-2018-0063","article-title":"Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major","volume":"13","author":"Mehrizi","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_174","first-page":"5341","article-title":"An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis","volume":"9","author":"Ribeiro","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.2147\/IJN.S220410","article-title":"Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of Leishmania major: Real-time PCR assay plus","volume":"14","author":"Mehrizi","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Zadeh Mehrizi, T., Shafiee Ardestani, M., Haji Molla Hoseini, M., Khamesipour, A., Mosaffa, N., and Ramezani, A. (2018). Novel Nanosized Chitosan-Betulinic Acid against Resistant Leishmania Major and First Clinical Observation of such parasite in Kidney. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30103-7"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2217\/nnm-2019-0320","article-title":"Rifampicin-loaded nanotransferosomal gel for treatment of cutaneous leishmaniasis: Passive targeting via topical route","volume":"15","author":"Rabia","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.nano.2015.07.011","article-title":"Assessment of \u03b2-lapachone loaded in lecithin-chitosan nanoparticles for the topical treatment of cutaneous leishmaniasis in L. major infected BALB\/c mice","volume":"11","author":"Moreno","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.niox.2021.04.008","article-title":"Nitric-oxide releasing chitosan nanoparticles towards effective treatment of cutaneous leishmaniasis","volume":"113\u2013114","author":"Cabral","year":"2021","journal-title":"Nitric Oxide"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41573-023-00822-2","article-title":"Drugging the NLRP3 inflammasome: From signalling mechanisms to therapeutic targets","volume":"23","author":"Lamkanfi","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/imr.12886","article-title":"Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis","volume":"297","author":"Harrington","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.mib.2019.05.005","article-title":"Inflammasomes and Leishmania: In good times or bad, in sickness or in health","volume":"52","author":"Zamboni","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1096\/fj.201700407R","article-title":"Leishmania donovani inhibits inflammasome-dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2","volume":"31","author":"Gupta","year":"2017","journal-title":"FASEB J."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Khadir, F., Shaler, C.R., Oryan, A., Rudak, P.T., Mazzuca, D.M., Taheri, T., Dikeakos, J.D., Haeryfar, S.M.M., and Rafati, S. (2018). Therapeutic control of leishmaniasis by inhibitors of the mammalian target of rapamycin. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006701"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"108976","DOI":"10.1016\/j.vetpar.2019.108976","article-title":"Antileishmanial effect of rapamycin as an alternative approach to control Leishmania tropica infection","volume":"276","author":"Khadir","year":"2019","journal-title":"Vet. Parasitol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1073\/pnas.1110339109","article-title":"Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis","volume":"109","author":"Cummings","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jid.2023.09.280","article-title":"The \u03b2-Carboline Harmine Has a Protective Immunomodulatory Role in Nonhealing Cutaneous Leishmaniasis","volume":"144","author":"Peyvandi","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jid.2020.07.011","article-title":"Granzyme B inhibition by tofacitinib blocks pathology induced by CD8 T cells in cutaneous leishmaniasis","volume":"141","author":"Novais","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1182\/blood-2013-06-507947","article-title":"Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes","volume":"122","author":"Dubovsky","year":"2013","journal-title":"Blood"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1128\/MCB.00086-12","article-title":"The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection","volume":"32","author":"Wetzel","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3934\/microbiol.2020010","article-title":"Study of therapeutic effect of different concentrations of imatinib on Balb\/c model of cutaneous leishmaniasis","volume":"6","author":"Moslehi","year":"2020","journal-title":"AIMS Microbiol."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Modolell, M., Choi, B.-S., Ryan, R.O., Hancock, M., Titus, R.G., Abebe, T., Hailu, A., M\u00fcller, I., Rogers, M.E., and Bangham, C.R.M. (2009). Local Suppression of T Cell Responses by Arginase-Induced L-Arginine Depletion in Nonhealing Leishmaniasis. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000480"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e12691","DOI":"10.1111\/pim.12691","article-title":"The outcome of arginase activity inhibition in BALB\/c mice hosting Leishmania tropica","volume":"42","author":"Nahidi","year":"2020","journal-title":"Parasite Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"6085","DOI":"10.1128\/IAI.73.9.6085-6090.2005","article-title":"Arginase I Induction during Leishmania major Infection Mediates the Development of Disease","volume":"73","author":"Iniesta","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3923\/ijbc.2015.110.122","article-title":"Partial Immunotherapy of Leishmaniasis by in vivo Trial of L-Arginine in Balb\/c Mice Infected with Leishmania major via Nitric Oxide Pathway","volume":"9","author":"Faezi","year":"2015","journal-title":"Int. J. Biol. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1590\/S0074-02762000000400006","article-title":"Action of pentoxifylline on experimental cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis","volume":"95","author":"Oliveira","year":"2000","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.exppara.2010.12.003","article-title":"Influence of long-term treatment with pravastatin on the survival, evolution of cutaneous lesion and weight of animals infected by Leishmania amazonensis","volume":"127","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.exppara.2013.01.020","article-title":"Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB\/c mice","volume":"134","author":"Tosta","year":"2013","journal-title":"Exp. Parasitol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Parihar, S.P., Hartley, M.-A., Hurdayal, R., Guler, R., and Brombacher, F. (2016). Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice. Sci. Rep., 6.","DOI":"10.1038\/srep33458"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Martins, S.S., Barroso, D.H., Rodrigues, B.C., da Motta, J.d.O.C., Freire, G.S.M., Pereira, L.I.d.A., Kurisky, P.S., Gomes, C.M., and Sampaio, R.N.R. (2021). A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated with Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.700323"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Castro, M.d.M., Cossio, A., Navas, A., Fernandez, O., Valderrama, L., Cuervo-Pardo, L., Marquez-O\u00f1ate, R., G\u00f3mez, M.A., and Saravia, N.G. (2022). Pentoxifylline in the Treatment of Cutaneous Leishmaniasis: A Randomized Clinical Trial in Colombia. Pathogens, 11.","DOI":"10.3390\/pathogens11030378"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1086\/511643","article-title":"Oral Pentoxifylline Combined with Pentavalent Antimony: A Randomized Trial for Mucosal Leishmaniasis","volume":"44","author":"Machado","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.4269\/ajtmh.16-0435","article-title":"Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis","volume":"96","author":"Brito","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4269\/ajtmh.2001.65.87","article-title":"Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony","volume":"65","author":"Lessa","year":"2001","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/jac\/dkw448","article-title":"Pharmacological inhibition of p110\u03b4 subunit of PI3K confers protection against experimental leishmaniasis","volume":"72","author":"Khadem","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jid.2020.08.033","article-title":"Identifying a Potential Therapeutic Host Target in Cutaneous Leishmaniasis","volume":"141","author":"Croitoru","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_207","unstructured":"Machado, P.R.L. (2024, August 21). Tofacitinib Associated with Meglumine Antimoniate in the Control of American Tegumentary Leishmaniasis. A Randomized and Controlled Clinical Trial; clinicaltrials.gov; Report No.: NCT06011343. August 2023, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06011343."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/infdis\/jiu455","article-title":"Arginase I, Polyamine, and Prostaglandin E2 Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis","volume":"211","author":"Boaventura","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1016\/j.bmc.2019.07.022","article-title":"Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity","volume":"27","author":"Maquiaveli","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_210","first-page":"21","article-title":"Inhibition of Murine Systemic Leishmaniasis by Acetyl Salicylic Acid via Nitric Oxide Immunomodulation","volume":"7","author":"Nahrevanian","year":"2012","journal-title":"Iran. J. Parasitol."},{"key":"ref_211","first-page":"269","article-title":"In-Vitro and In-Vivo Activities of Phenolic Compounds Against Cutaneous Leishmaniasis","volume":"10","author":"Monzote","year":"2016","journal-title":"Rec. Nat. Prod."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.00807-20","article-title":"Gallic and Ellagic Acids Are Promising Adjuvants to Conventional Amphotericin B for the Treatment of Cutaneous Leishmaniasis","volume":"64","author":"Alves","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Bilbao-Ramos, P., Serrano, D.R., Ruiz Salda\u00f1a, H.K., Torrado, J.J., Bol\u00e1s-Fern\u00e1ndez, F., and Dea-Ayuela, M.A. (2020). Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis. Molecules, 25.","DOI":"10.3390\/molecules25061394"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/jac\/dkac007","article-title":"Effect of topical berberine in murine cutaneous leishmaniasis lesions","volume":"77","author":"Calvo","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1128\/AAC.02804-15","article-title":"A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways","volume":"60","author":"McChesney","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0035-9203(00)90341-9","article-title":"A topical nitric oxide-generating therapy for cutaneous leishmaniasis","volume":"94","author":"Davidson","year":"2000","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00210-017-1387-y","article-title":"Gallic and ellagic acids: Two natural immunomodulator compounds solve infection of macrophages by Leishmania major","volume":"390","author":"Alves","year":"2017","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3389\/fimmu.2017.00893","article-title":"Effects of Bone Marrow Mesenchymal Stromal Cell Therapy in Experimental Cutaneous Leishmaniasis in BALB\/c Mice Induced by Leishmania amazonensis","volume":"8","author":"Pereira","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jgar.2020.09.005","article-title":"Therapeutic effects of mesenchymal stem cells on cutaneous leishmaniasis lesions caused by Leishmania major","volume":"23","author":"Navard","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.1128\/IAI.72.8.4455-4463.2004","article-title":"CD4+ Th1 cells induced by dendritic cell-based immunotherapy in mice chronically infected with Leishmania amazonensis do not promote healing","volume":"72","author":"Vanloubbeeck","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1590\/S0037-86822006000100003","article-title":"Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment","volume":"39","author":"Mayrink","year":"2006","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_222","first-page":"657016","article-title":"Clinical and Immunological Analysis of Cutaneous Leishmaniasis before and after Different Treatments","volume":"2013","author":"Spinetti","year":"2013","journal-title":"J. Parasitol. Res."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1046\/j.1365-3024.2000.00278.x","article-title":"Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1-like response in American cutaneous leishmaniasis patients","volume":"22","author":"Cabrera","year":"2000","journal-title":"Parasite Immunol."},{"key":"ref_224","first-page":"365","article-title":"Immunological correlates of cure in the first American Cutaneous Leishmaniasis patient treated by immunotherapy in Argentina: A case report","volume":"52","author":"Barrio","year":"2011","journal-title":"Investig. Cl\u00edn."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1590\/S0074-02762004000100010","article-title":"Therapy of Venezuelan patients with severe mucocutaneous or early lesions of diffuse cutaneous leishmaniasis with a vaccine containing pasteurized Leishmania promastigotes and bacillus Calmette-Guerin: Preliminary report","volume":"99","author":"Convit","year":"2004","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0035-9203(03)90093-9","article-title":"Immunotherapy of American cutaneous leishmaniasis in Venezuela during the period 1990\u20131999","volume":"97","author":"Convit","year":"2003","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_227","first-page":"223","article-title":"Treatment of Experimental Cutaneous Leishmaniasis by the Therapeutic Vaccine SLA-R848-Pam3CSK4","volume":"12","author":"Katebi","year":"2021","journal-title":"J. Clin. Cell. Immunol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1590\/S1413-86702001000400008","article-title":"Successful use of a defined antigen\/GM-CSF adjuvant vaccine to treat mucosal leishmaniasis refractory to antimony: A case report","volume":"5","author":"Badaro","year":"2001","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1086\/507708","article-title":"Immunotherapy for Drug-Refractory Mucosal Leishmaniasis","volume":"194","author":"Badaro","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.4049\/jimmunol.1000238","article-title":"Applying TLR Synergy in Immunotherapy: Implications in Cutaneous Leishmaniasis","volume":"185","author":"Raman","year":"2010","journal-title":"J. Immunol."},{"key":"ref_231","first-page":"3011","article-title":"Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy against Leishmania amazonensis Murine Infection","volume":"5","author":"Nico","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1016\/S0264-410X(00)00109-2","article-title":"Therapy of murine cutaneous leishmaniasis by DNA vaccination","volume":"18","author":"Handman","year":"2000","journal-title":"Vaccine"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1016\/j.ymthe.2021.03.020","article-title":"Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan","volume":"29","author":"Younis","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1046\/j.1365-4362.2002.01336.x","article-title":"Immunochemotherapy for cutaneous leishmaniasis: A controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial","volume":"41","author":"Pinto","year":"2002","journal-title":"Int. J. Dermatol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1590\/S0074-02762001000100010","article-title":"Immunochemotherapy in American cutaneous leishmaniasis: Immunological aspects before and after treatment","volume":"96","author":"Toledo","year":"2001","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"378","DOI":"10.4269\/ajtmh.2009.81.378","article-title":"Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG\/Leishmania antigens","volume":"81","author":"Pereira","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.trstmh.2007.08.006","article-title":"Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: A novel approach to treatment","volume":"102","author":"Musa","year":"2008","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1016\/j.vaccine.2010.07.063","article-title":"A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with meglumine antimoniate for the treatment of cutaneous leishmaniasis","volume":"28","author":"Nascimento","year":"2010","journal-title":"Vaccine"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"708391","DOI":"10.1155\/2013\/708391","article-title":"Treatment-Based Strategy for the Management of Post-Kala-Azar Dermal Leishmaniasis Patients in the Sudan","volume":"2013","author":"Musa","year":"2013","journal-title":"J. Trop. Med."},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Chaves, L.F., and Pascual, M. (2006). Climate Cycles and Forecasts of Cutaneous Leishmaniasis, a Nonstationary Vector-Borne Disease. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030295"},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, C., Wang, O., Strutz, S.E., Gonz\u00e1lez-Salazar, C., S\u00e1nchez-Cordero, V., and Sarkar, S. (2010). Climate Change and Risk of Leishmaniasis in North America: Predictions from Ecological Niche Models of Vector and Reservoir Species. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000585"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Ponte-Sucre, A., Gamarro, F., Dujardin, J.-C., Barrett, M.P., L\u00f3pez-V\u00e9lez, R., Garc\u00eda-Hern\u00e1ndez, R., Pountain, A.W., Mwenechanya, R., and Papadopoulou, B. (2017). Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006052"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.4049\/jimmunol.168.4.1659","article-title":"CpG Oligodeoxynucleotides as Vaccine Adjuvants in Primates1","volume":"168","author":"Verthelyi","year":"2002","journal-title":"J. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/10\/1179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:14:57Z","timestamp":1760112897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/10\/1179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":243,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["vaccines12101179"],"URL":"https:\/\/doi.org\/10.3390\/vaccines12101179","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,17]]}}}