{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T02:27:05Z","timestamp":1785032825722,"version":"3.55.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Leishmaniasis includes a spectrum of diseases ranging from debilitating cutaneous to fatal visceral infections. This disease is caused by the parasitic protozoa of the genus<jats:italic>Leishmania<\/jats:italic>that is transmitted by infected sandflies. Over 1 billion people are at risk of leishmaniasis with an annual incidence of over 2 million cases throughout tropical and subtropical regions in close to 100 countries. Leishmaniasis is the only human parasitic disease where vaccination has been successful through a procedure known as leishmanization that has been widely used for decades in the Middle East. Leishmanization involved intradermal inoculation of live<jats:italic>Leishmania major<\/jats:italic>parasites resulting in a skin lesion that following natural healing provided protective immunity to re-infection. Leishmanization is however no longer practiced due to safety and ethical concerns that the lesions at the site of inoculation that can last for months in some people. New genome editing technologies involving CRISPR has now made it possible to engineer safer attenuated strains of<jats:italic>Leishmania<\/jats:italic>, which induce protective immunity making way for a second generation leishmanization that can enter into human trials. A major consideration will be how the test the efficacy of a vaccine in the midst of the visceral leishmaniasis elimination program. One solution will be to use the leishmanin skin test (LST) that was also used for decades to determine exposure and immunity to Leishmania. The LST involves injection of antigen from<jats:italic>Leishmania<\/jats:italic>in the skin dermis resulting in a delayed type hypersensitivity (DTH) immune reaction associated with a Th1 immune response and protection against visceral leishmaniasis. Reintroduction of novel approaches for leishmanization and the leishmanin skin test can play a major role in eliminating leishmaniasis.<\/jats:p>","DOI":"10.3389\/fcimb.2021.639801","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T05:24:09Z","timestamp":1615958649000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["Revival of Leishmanization and Leishmanin"],"prefix":"10.3389","volume":"11","author":[{"given":"Thalia","family":"Pacheco-Fernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Volpedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreenivas","family":"Gannavaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parna","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranadhir","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Satoskar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Matlashewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira L.","family":"Nakhasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1002\/1521-4141(200010)30:10<2935::AID-IMMU2935>3.0.CO;2-Q","article-title":"Endogenous IL-4 is necessary for effective drug therapy against visceral leishmaniasis","volume":"30","author":"Alexander","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.clim.2006.01.017","article-title":"Elevated levels of interferon-\u03b3, interleukin-10, and interleukin-6 during active disease in Indian kala azar","volume":"119","author":"Ansari","year":"2006","journal-title":"Clin. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3977","DOI":"10.4049\/jimmunol.1003588","article-title":"IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis","volume":"186","author":"Ansari","year":"2011","journal-title":"J. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41467-020-20569-3","article-title":"Characterization of a new Leishmania major strain for use in a controlled human infection model","volume":"12","author":"Ashwin","year":"2021","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/srep33059","article-title":"Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs","volume":"6","author":"Avishek","year":"2016","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0035-9203(01)90344-X","article-title":"Interleukin-13 in Iranian patients with visceral leishmaniasis: relationship to other Th2 and Th1 cytokines","volume":"95","author":"Babaloo","year":"2001","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1006\/cyto.2000.0694","article-title":"IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis","volume":"12","author":"Bacellar","year":"2000","journal-title":"Cytokine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"163","DOI":"10.4049\/jimmunol.1700674","article-title":"Live Attenuated","volume":"200","author":"Banerjee","year":"2018","journal-title":"J. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"744","DOI":"10.4269\/ajtmh.2006.75.744","article-title":"Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal study of visceral leishmaniasis in Bangladesh","volume":"75","author":"Bern","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1111\/bjd.12205","article-title":"Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India","volume":"168","author":"Bumb","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.4049\/jimmunol.1701582","article-title":"Distinct roles for CD4+ Foxp3+ regulatory T cells and IL-10\u2013mediated immunoregulatory mechanisms during experimental visceral Leishmaniasis caused by Leishmania donovani","volume":"201","author":"Bunn","year":"2018","journal-title":"J. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-5-113","article-title":"Balance of IL-10 and interferon-\u03b3 plasma levels in human visceral leishmaniasis: implications in the pathogenesis","volume":"5","author":"Caldas","year":"2005","journal-title":"BMC Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/j.humimm.2010.09.002","article-title":"Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis","volume":"71","author":"Campanelli","year":"2010","journal-title":"Hum. Immunol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-529","article-title":"Immunologic response and memory T cells in subjects cured of tegumentary leishmaniasis","volume":"13","author":"Carvalho","year":"2013","journal-title":"BMC Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005951","article-title":"Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis","volume":"11","author":"Cec\u00edlio","year":"2017","journal-title":"PloS Negl. Trop. Dis."},{"key":"B16","unstructured":"Leishmaniasis2020"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007216","article-title":"Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study","volume":"13","author":"Chakravarty","year":"2019","journal-title":"PloS Negl. Trop. Dis."},{"key":"B19","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.4049\/jimmunol.138.11.3688","article-title":"Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones","volume":"138","author":"Cher","year":"1987","journal-title":"J. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1038\/cti.2015.6","article-title":"From mouse to man: safety, immunogenicity and efficacy of a candidate leishmaniasis vaccine LEISH-F3+GLA-SE","volume":"4","author":"Coler","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.4049\/jimmunol.1000483","article-title":"The early generation of a heterogeneous CD4+ T cell response to Leishmania major","volume":"185","author":"Colpitts","year":"2010","journal-title":"J. Immunol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000943","article-title":"Vaccines for the leishmaniases: proposals for a research agenda","volume":"5","author":"Costa","year":"2011","journal-title":"PloS Negl. Trop. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nm1592","article-title":"Multifunctional TH 1 cells define a correlate of vaccine-mediated protection against Leishmania major","volume":"13","author":"Darrah","year":"2007","journal-title":"Nat. Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00670","article-title":"Cytokines: Key Determinants of Resistance or Disease Progression in Visceral Leishmaniasis: Opportunities for Novel Diagnostics and Immunotherapy","volume":"10","author":"Dayakar","year":"2019","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/CVI.00108-17","article-title":"Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis","volume":"24","author":"Duthie","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41541-017-0025-5","article-title":"A defined subunit vaccine that protects against vector-borne visceral leishmaniasis","volume":"2","author":"Duthie","year":"2017","journal-title":"NPJ Vaccines"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02420","article-title":"Heterologous Immunization With Defined RNA and Subunit Vaccines Enhances T Cell Responses That Protect Against","volume":"9","author":"Duthie","year":"2018","journal-title":"Front. Immunol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00393","article-title":"Phenotypic and Functional Profiles of Antigen-Specific CD4+ and CD8+ T Cells Associated with Infection Control in Patients with Cutaneous Leishmaniasis","volume":"8","author":"Egui","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02273","article-title":"miR-21 Expression Determines the Early Vaccine Immunity Induced by","volume":"10","author":"Gannavaram","year":"2019","journal-title":"Front. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1111\/j.1365-2133.2009.09573.x","article-title":"Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1\/T cytotoxic type 1 cells","volume":"162","author":"Geiger","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/pim.12156","article-title":"Characterization of micro RNA expression profiles in L eishmania-infected human phagocytes","volume":"37","author":"Geraci","year":"2015","journal-title":"Parasite Immunol."},{"key":"B32","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":"B33","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.chom.2013.02.005","article-title":"Leishmania donovani targets Dicer1 to downregulate miR-122, lower serum cholesterol, and facilitate murine liver infection","volume":"13","author":"Ghosh","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1093\/infdis\/jis771","article-title":"Successful therapy of visceral leishmaniasis with curdlan involves T-helper 17 cytokines","volume":"207","author":"Ghosh","year":"2013","journal-title":"J.\u00a0Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.cellimm.2016.07.010","article-title":"Memory T cells in cutaneous leishmaniasis","volume":"309","author":"Glennie","year":"2016","journal-title":"Cell. Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1084\/jem.20142101","article-title":"Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection","volume":"212","author":"Glennie","year":"2015","journal-title":"J. Exp. Med."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006349","article-title":"Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes","volume":"13","author":"Glennie","year":"2017","journal-title":"PloS Pathog."},{"key":"B38","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.pt.2005.06.007","article-title":"Insights into CD4+ memory T cells following Leishmania infection","volume":"21","author":"Gollob","year":"2005","journal-title":"Trends Parasitol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01437","article-title":"The equivocal role of Th17 cells and neutrophils on immunopathogenesis of leishmaniasis","volume":"8","author":"Gon\u00e7alves-de-Albuquerque","year":"2017","journal-title":"Front. Immunol."},{"key":"B40","first-page":"155","article-title":"Mechanisms of immune evasion in leishmaniasis","volume-title":"Adv. Appl. Microbiol.","author":"Gupta","year":"2013"},{"key":"B41","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.clim.2005.06.015","article-title":"T cell subset and cytokine profiles in human visceral leishmaniasis during active and asymptomatic or sub-clinical infection with Leishmania donovani","volume":"117","author":"Hailu","year":"2005","journal-title":"Clin. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.pt.2019.04.002","article-title":"CD4+ T cell-mediated immunity against the phagosomal pathogen Leishmania: Implications for vaccination","volume":"35","author":"Hohman","year":"2019","journal-title":"Trends Parasitol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1080\/14760584.2018.1459191","article-title":"Vaccine candidates against leishmania under current research","volume":"17","author":"Iborra","year":"2018","journal-title":"Expert Rev. Vaccines"},{"key":"B44","first-page":"144","article-title":"Immunization with second generation Leishmania vaccine, L major Centrin deleted parasites induces skin resident memory T cells that play a role in protection against infection","author":"Ismail","year":"2020"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/2020.11.18.388553","article-title":"Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasis","author":"Karmakar","year":"2020","journal-title":"bioRxiv"},{"key":"B47","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.smim.2013.04.006","article-title":"Tuberculosis vaccines: time to think about the next generation","volume":"25","author":"Kaufmann","year":"2013","journal-title":"Semin. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: complexity at the host-pathogen interface","volume":"9","author":"Kaye","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00281-020-00788-y","article-title":"Leishmaniasis immunopathology-impact on design and use of vaccines, diagnostics and drugs","volume":"42","author":"Kaye","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.4161\/hv.7.11.17752","article-title":"Leishmaniasis","volume":"7","author":"Kedzierski","year":"2011","journal-title":"Hum. Vaccin."},{"key":"B501","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838423.","article-title":"Decreased IL-10 and IL-13 production and increased CD44hi T cell recruitment contribute to Leishmania major immunity induced by non-persistent parasites","volume":"38","author":"Kedzierski","year":"2008","journal-title":"Eur J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003451","article-title":"miR-182 and miR-10a are key regulators of Treg specialisation and stability during Schistosome and Leishmania-associated inflammation","volume":"9","author":"Kelada","year":"2013","journal-title":"PloS Pathog."},{"key":"B52","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1046\/j.1365-3156.2002.00832.x","article-title":"Epidemiology and clinical manifestations of Leishmania donovani infection in two villages in an endemic area in eastern Sudan","volume":"7","author":"Khalil","year":"2002","journal-title":"Trop. Med. Int. Health"},{"key":"B53","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1016\/j.vaccine.2005.02.015","article-title":"Leishmanization: use of an old method for evaluation of candidate vaccines against leishmaniasis","volume":"23","author":"Khamesipour","year":"2005","journal-title":"Vaccine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.4049\/jimmunol.0802860","article-title":"IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis","volume":"182","author":"Khouri","year":"2009","journal-title":"J. Immunol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"30","DOI":"10.4103\/tp.TP_32_18","article-title":"Prophylactic interferon-\u03b3 and interleukin-17 facilitate parasite clearance in experimental visceral leishmaniasis","volume":"9","author":"Kumar","year":"2019","journal-title":"Trop. Parasitol."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01716","article-title":"Differential Regulation of miRNA Profiles of Human Cells Experimentally Infected by Leishmania donovani Isolated From Indian Visceral Leishmaniasis and Post-Kala-Azar Dermal Leishmaniasis","volume":"11","author":"Kumar","year":"2020","journal-title":"Front. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/cyto.a.20256","article-title":"Multiplex analysis of circulating cytokines in the sera of patients with different clinical forms of visceral leishmaniasis","volume":"69","author":"Kurkjian","year":"2006","journal-title":"Cytometry Part A"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002478","article-title":"MicroRNA expression profile in human macrophages in response to Leishmania major infection","volume":"7","author":"Lemaire","year":"2013","journal-title":"PloS Negl. Trop. Dis."},{"key":"B59","first-page":"1340","article-title":"Skin-resident T cells keep parasites on a Leish","volume-title":"J Exp Med","author":"Mackay","year":"2015"},{"key":"B60","doi-asserted-by":"publisher","first-page":"5858","DOI":"10.4049\/jimmunol.164.11.5858","article-title":"IL-12p70 production by Leishmania major-harboring human dendritic cells is a CD40\/CD40 ligand-dependent process","volume":"164","author":"Marovich","year":"2000","journal-title":"J. Immunol."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00883","article-title":"Leishmania Hijacks Myeloid Cells for Immune Escape","volume":"9","author":"Mart\u00ednez-L\u00f3pez","year":"2018","journal-title":"Front. Microbiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.vaccine.2012.11.065","article-title":"Leishmanization revisited: immunization with a naturally attenuated cutaneous Leishmania donovani isolate from Sri Lanka protects against visceral leishmaniasis","volume":"31","author":"McCall","year":"2013","journal-title":"Vaccine"},{"key":"B63","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/infdis\/jir080","article-title":"Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4R\u03b1\u2013responsive macrophages and neutrophils","volume":"204","author":"McFarlane","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2020.107846","article-title":"Characterization of serum cytokines and circulating microRNAs that are predicted to regulate inflammasome genes in cutaneous leishmaniasis patients","volume":"210","author":"Mendon\u00e7a","year":"2020","journal-title":"Exp. Parasitol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cyto.2018.07.001","article-title":"The impact of IL-10 dynamic modulation on host immune response against visceral leishmaniasis","volume":"112","author":"Mesquita","year":"2018","journal-title":"Cytokine"},{"key":"B66","doi-asserted-by":"publisher","first-page":"95","DOI":"10.4103\/ijpvm.IJPVM_116_18","article-title":"Vaccines Entered in Clinical Trials: A Review of Literature","volume":"10","author":"Moafi","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2019.105173","article-title":"An overview of leishmanization experience: A successful control measure and a tool to evaluate candidate vaccines","volume":"200","author":"Mohebali","year":"2019","journal-title":"Acta Trop."},{"key":"B68","first-page":"323","article-title":"A cutis-rea\u00e7\u00e3o na leishmaniose","volume":"1","author":"Montenegro","year":"1926","journal-title":"An. Fac. Med. Sao Paulo"},{"key":"B69","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/j.1600-065X.2010.00983.x","article-title":"Cell biology and immunology of Leishmania","volume":"240","author":"Mougneau","year":"2011","journal-title":"Immunol. Rev."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/pim.12783","article-title":"Status of IL-4 and IL-10 driven markers in experimental models of Visceral Leishmaniasis","volume":"43","author":"Moulik","year":"2020","journal-title":"Parasite Immunol."},{"key":"B71","doi-asserted-by":"publisher","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":"B72","first-page":"377","article-title":"Effectiveness of leishmanization in the control of cutaneous leishmaniasis","volume":"76","author":"Nadim","year":"1983","journal-title":"Bull. Soc. Pathol. Exot. Filiales"},{"key":"B73","doi-asserted-by":"publisher","first-page":"8088","DOI":"10.4049\/jimmunol.0803720","article-title":"Neutrophils and macrophages cooperate in host resistance against\u00a0Leishmania braziliensis\u00a0infection","volume":"183","author":"Novais","year":"2009","journal-title":"J. Immunol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.it.2007.07.004","article-title":"Interleukin-10 and the pathogenesis of human visceral leishmaniasis","volume":"28","author":"Nyl\u00e9n","year":"2007","journal-title":"Trends Immunol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1084\/jem.20061141","article-title":"Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+ CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis","volume":"204","author":"Nyl\u00e9n","year":"2007","journal-title":"J. Exp. Med."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005527","article-title":"A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH","volume":"11","author":"Osman","year":"2017","journal-title":"PloS Negl. Trop. Dis."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00206","article-title":"Differential expression of miRNA regulates T cell differentiation and plasticity during visceral leishmaniasis infection","volume":"7","author":"Pandey","year":"2016","journal-title":"Front. Microbiol."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000484","article-title":"Vector transmission of leishmania abrogates vaccine-induced protective immunity","volume":"5","author":"Peters","year":"2009","journal-title":"PloS Pathog."},{"key":"B78","doi-asserted-by":"publisher","first-page":"4832","DOI":"10.4049\/jimmunol.1201676","article-title":"Evaluation of recombinant Leishmania polyprotein plus glucopyranosyl lipid A stable emulsion vaccines against sand fly-transmitted Leishmania major in C57BL\/6 mice","volume":"189","author":"Peters","year":"2012","journal-title":"J. Immunol."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004538","article-title":"Chronic parasitic infection maintains high frequencies of short-lived Ly6C+ CD4+ effector T cells that are required for protection against re-infection","volume":"10","author":"Peters","year":"2014","journal-title":"PloS Pathog."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1172\/JCI38813","article-title":"IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani","volume":"119","author":"Pitta","year":"2009","journal-title":"J. Clin. Invest."},{"key":"B82","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/0008-8749(82)90036-3","article-title":"Immunohistological analysis of delayed-type hypersensitivity in man","volume":"74","author":"Poulter","year":"1982","journal-title":"Cell Immunol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1093\/infdis\/173.3.699","article-title":"Differential expression of chemokines in patients with localized and diffuse cutaneous American leishmaniasis","volume":"173","author":"Ritter","year":"1996","journal-title":"J. Infect. Dis."},{"key":"B84","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/eji.1830210307","article-title":"Immunobiological studies on experimental visceral leishmaniasis I. Changes in lymphoid organs and their possible role in pathogenesis","volume":"21","author":"Saha","year":"1991","journal-title":"Eur. J. Immunol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"4894","DOI":"10.1128\/IAI.63.12.4894-4899.1995","article-title":"Disruption of the murine interleukin-4 gene inhibits disease progression during Leishmania mexicana infection but does not increase control of Leishmania donovani infection","volume":"63","author":"Satoskar","year":"1995","journal-title":"Infect. Immun."},{"key":"B87","doi-asserted-by":"publisher","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":"B86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/cshperspect.a038059","article-title":"Long-Lived Skin-Resident Memory T Cells Contribute to Concomitant Immunity in Cutaneous Leishmaniasis","volume":"12","author":"Scott","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01227","article-title":"Translating Observations From Leishmanization Into Non-Living Vaccines: The Potential of Dendritic Cell-Based Vaccination Strategies Against","volume":"9","author":"Seyed","year":"2018","journal-title":"Front. Immunol."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00019","article-title":"Turning 21: Induction of miR-21 as a Key Switch in the Inflammatory Response","volume":"6","author":"Sheedy","year":"2015","journal-title":"Front. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00005-008-0010-9","article-title":"Live attenuated Leishmania vaccines: a potential strategic alternative","volume":"56","author":"Silvestre","year":"2008","journal-title":"Arch. Immunol. Ther. Exp. (Warsz)"},{"key":"B91","doi-asserted-by":"publisher","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":"B92","doi-asserted-by":"publisher","first-page":"4804","DOI":"10.1128\/IAI.71.8.4804-4807.2003","article-title":"Both interleukin-4 (IL-4) and IL-4 receptor \u03b1 signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity","volume":"71","author":"St\u00e4ger","year":"2003","journal-title":"Infect. Immun."},{"key":"B500","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1080\/14787210.2018.1532790","article-title":"Visceral leishmaniasis elimination targets in India, strategies for preventing resurgence","volume":"16","author":"Sundar","year":"2018","journal-title":"Expert Rev. Anti. Infect Ther."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1096\/fj.15-277202","article-title":"IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani","volume":"30","author":"Terrazas","year":"2016","journal-title":"FASEB J."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00314","article-title":"Identification and characterization of miRNAs in response to Leishmania donovani infection: delineation of their roles in macrophage dysfunction","volume":"8","author":"Tiwari","year":"2017","journal-title":"Front. Microbiol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1007\/s10875-012-9788-7","article-title":"CCR7+ central and CCR7\u2013 effector memory CD4+ T cells in human cutaneous leishmaniasis","volume":"33","author":"Valian","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010107","article-title":"Quantification of parasite load in clinical samples of leishmaniasis patients: IL-10 level correlates with parasite load in visceral leishmaniasis","volume":"5","author":"Verma","year":"2010","journal-title":"PloS One"},{"key":"B97","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.imlet.2006.08.002","article-title":"Mantoux Test as a model for a secondary immune response in humans","volume":"107","author":"Vukmanovic-Stejic","year":"2006","journal-title":"Immunol. Lett."},{"key":"B98","unstructured":"Leishmaniasis2020"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2020.107849","article-title":"The potential of live attenuated vaccines against Cutaneous Leishmaniasis","volume":"210","author":"Zabala-Pe\u00f1afiel","year":"2020","journal-title":"Exp. Parasit."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/nm1108","article-title":"Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites","volume":"10","author":"Zaph","year":"2004","journal-title":"Nat. Med."},{"key":"B101","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.1038\/s41467-020-17154-z","article-title":"A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"B102","doi-asserted-by":"publisher","first-page":"826","DOI":"10.4269\/ajtmh.1994.51.826","article-title":"Endemic kala-azar in eastern Sudan: a longitudinal study on the incidence of clinical and subclinical infection and post-kala-azar dermal leishmaniasis","volume":"51","author":"Zijlstra","year":"1994","journal-title":"Am. J. Trop. Med. Hyg."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.639801\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T07:57:19Z","timestamp":1698047839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.639801\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":103,"alternative-id":["10.3389\/fcimb.2021.639801"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.639801","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,17]]},"article-number":"639801"}}