{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:30:31Z","timestamp":1774618231292,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Direcci\u00f3n General de Universidades e Investigaci\u00f3n\n\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/03mnxvp33"},{"name":"Junta de Castilla y Le\u00f3n\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/02s8dab97","award":["LE017-G24"],"award-info":[{"award-number":["LE017-G24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A wide range of Leishmania species, transmitted by phlebotomine, cause leishmaniasis, which presents diverse clinical manifestations. Leishmaniasis has a high impact on vulnerable communities, primarily affecting people suffering from malnutrition or poor housing. Because leishmaniasis is associated with poverty, access to treatment is limited. In addition, high drug toxicity and therapeutic failure, related to drug resistance, remain major challenges. Therefore, there is a need to develop new therapeutic approaches that are safer and more effective. Drug combinations and repurposing are two strategies used in the development of treatments. The combination of drugs with different mechanisms of action can minimise resistance and allow dose reduction, increasing the likelihood of successful drug repurposing. This study evaluated the antileishmanial effects of combining antitumoral agents (paclitaxel and docetaxel) with standard drugs (miltefosine and paromomycin). Results demonstrated synergistic effects at higher doses. Furthermore, the antitumoral compounds enhanced the host immune response by promoting macrophage polarisation toward the M1 phenotype, essential for parasite control. These findings highlight a promising approach that could improve efficacy and reduce resistance.<\/jats:p>","DOI":"10.3390\/ijms27073055","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"3055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antileishmanial and Immunomodulatory Activity of Paclitaxel and Docetaxel Combined with Miltefosine and Paromomycin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-060X","authenticated-orcid":false,"given":"Estela","family":"Melc\u00f3n-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-6116","authenticated-orcid":false,"given":"Rafael","family":"Bala\u00f1a-Fouce","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-9669","authenticated-orcid":false,"given":"Carlos","family":"Garc\u00eda-Estrada","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9148-2997","authenticated-orcid":false,"given":"Rosa M.","family":"Reguera","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-8121","authenticated-orcid":false,"given":"Celia","family":"Fern\u00e1ndez-Rubio","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2001-6041","authenticated-orcid":false,"given":"Marta","family":"Cend\u00f3n-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda","family":"P\u00e9rez-Pertejo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"},{"name":"Instituto de Biomedicina (IBIOMED), Universidad de Le\u00f3n, Campus de Vegazana s\/n, 24071 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41572-025-00663-w","article-title":"Leishmaniasis","volume":"11","author":"Pareyn","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100995","DOI":"10.1016\/j.lanepe.2024.100995","article-title":"The potential of climatic suitability indicator for Leishmania transmission modelling in Europe: Insights and suggested directions","volume":"43","author":"Paz","year":"2024","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_3","unstructured":"(2026, February 24). Surveillance, Prevention and Control of Leishmaniases in the European Union and Its Neighbouring Countries. Available online: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/leishmaniasis-surveillance-eu.pdf."},{"key":"ref_4","unstructured":"(2026, February 24). Leishmaniasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1515\/pac-2018-1102","article-title":"Current and promising novel drug candidates against visceral leishmaniasis","volume":"91","author":"Reguera","year":"2019","journal-title":"Pure Appl. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1051\/parasite\/2025009","article-title":"Leishmaniases: Strategies in treatment development","volume":"32","author":"Majoor","year":"2025","journal-title":"Parasite"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.pt.2016.11.003","article-title":"Exploiting knowledge on Leishmania drug resistance to support the quest for new drugs","volume":"33","author":"Hefnawy","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11765","DOI":"10.1038\/s41598-018-30040-5","article-title":"Importance of secondary screening with clinical isolates for anti-leishmania drug discovery","volume":"8","author":"Hefnawy","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100617","DOI":"10.1016\/j.ijpddr.2025.100617","article-title":"Biological and molecular characterisation of in vitro selected miltefosine-resistant Leishmania amazonensis lines","volume":"29","author":"Neira","year":"2025","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13071-025-07105-2","article-title":"Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area","volume":"19","author":"Alcover","year":"2025","journal-title":"Parasit. Vectors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1021\/acsinfecdis.4c00693","article-title":"Advancing treatment for leishmaniasis: From overcoming challenges to embracing therapeutic innovations","volume":"11","author":"Singh","year":"2025","journal-title":"ACS Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1017\/S0031182016002523","article-title":"Chemotherapy of leishmaniasis: Present challenges","volume":"145","author":"Uliana","year":"2018","journal-title":"Parasitology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1016\/S1473-3099(23)00353-5","article-title":"The status of combination therapy for visceral leishmaniasis: An updated review","volume":"24","author":"Dorlo","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Melc\u00f3n-Fern\u00e1ndez, E., Galli, G., Garc\u00eda-Estrada, C., Bala\u00f1a-Fouce, R., Reguera, R.M., and P\u00e9rez-Pertejo, Y. (2023). Miltefosine and nifuratel combination: A promising therapy for the treatment of Leishmania donovani visceral leishmaniasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021635"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Melc\u00f3n-Fern\u00e1ndez, E., Galli, G., Bala\u00f1a-Fouce, R., Garc\u00eda-Fern\u00e1ndez, N., Mart\u00ednez-Valladares, M., Reguera, R.M., Garc\u00eda-Estrada, C., and P\u00e9rez-Pertejo, Y. (2024). In vitro and ex vivo synergistic effect of pyrvinium pamoate combined with miltefosine and paromomycin against Leishmania. Trop. Med. Infect. Dis., 9.","DOI":"10.3390\/tropicalmed9020030"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1021\/acsinfecdis.1c00139","article-title":"Ex vivo phenotypic screening of two small repurposing drug collections identifies nifuratel as a potential new treatment against visceral and cutaneous leishmaniasis","volume":"7","author":"Reguera","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0166-6851(00)00272-3","article-title":"Cellular effects of leishmanial tubulin inhibitors on L. donovani","volume":"110","author":"Havens","year":"2000","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dandugudumula, R., Fischer-Weinberger, R., and Zilberstein, D. (2022). Morphogenesis dynamics in Leishmania differentiation. Pathogens, 11.","DOI":"10.3390\/pathogens11090952"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s00436-002-0632-5","article-title":"Resistance to arsenite modulates expression of beta- and gamma-tubulin and sensitivity to paclitaxel during differentiation of Leishmania donovani","volume":"88","author":"Jayanarayan","year":"2002","journal-title":"Parasitol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1017\/S0031182005007687","article-title":"Altered tubulin dynamics, localization and post-translational modifications in sodium arsenite resistant Leishmania donovani in response to paclitaxel, trifluralin and a combination of both and induction of apoptosis-like cell death","volume":"131","author":"Jayanarayan","year":"2005","journal-title":"Parasitology"},{"key":"ref_22","doi-asserted-by":"crossref","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":"ref_23","doi-asserted-by":"crossref","first-page":"155297","DOI":"10.1016\/j.cyto.2020.155297","article-title":"A historical review of the role of cytokines involved in leishmaniasis","volume":"145","author":"Mirzaei","year":"2021","journal-title":"Cytokine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.pt.2021.07.003","article-title":"Leishmaniasis: The act of transmission","volume":"37","author":"Serafim","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alves, N.O., Oshiro, J.A., Silva, Y.C., Pacher, G.C., Casaril, A.E., Rizk, Y.S., Uehara, S.N.O., Paniago, A.M.M., Andrade, I.L.X., and Arruda, C.C.P. (2024). VL-HIV co-infection with Leishmania containing skin lesions resembling para-kala-azar dermal leishmaniasis. PLoS Negl. Trop. Dis., 18.","DOI":"10.1371\/journal.pntd.0012438"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.ijpara.2007.04.007","article-title":"The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist","volume":"37","author":"Kima","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1128\/IAI.66.9.4553-4556.1998","article-title":"Paclitaxel (Taxol)-induced killing of Leishmania major in murine macrophages","volume":"66","author":"Doherty","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.intimp.2003.08.007","article-title":"The immunopharmacology of paclitaxel (Taxol), docetaxel (Taxotere), and related agents","volume":"3","author":"Fitzpatrick","year":"2003","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1128\/AAC.02398-12","article-title":"Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay","volume":"57","author":"Hallyburton","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzyme Regul."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Almeida, F.S., Vanderley, S.E.R., Comberlang, F.C., Andrade, A.G., Cavalcante-Silva, L.H.A., Silva, E.D.S., Palmeira, P.H.S., Amaral, I.P.G.D., and Keesen, T.S.L. (2023). Leishmaniasis: Immune cells crosstalk in macrophage polarization. Trop. Med. Infect. Dis., 8.","DOI":"10.20944\/preprints202304.0903.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"155322","DOI":"10.1016\/j.cyto.2020.155322","article-title":"Cytokine saga in visceral leishmaniasis","volume":"147","author":"Bhor","year":"2021","journal-title":"Cytokine"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Samant, M., Sahu, U., Pandey, S.C., and Khare, P. (2021). Role of cytokines in experimental and human visceral leishmaniasis. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.624009"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.cellimm.2011.03.016","article-title":"IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection","volume":"270","author":"Petersen","year":"2011","journal-title":"Cell Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/erm.2024.36","article-title":"Chemokines signature and T cell dynamics in leishmaniasis: Molecular insight and therapeutic application","volume":"27","author":"Upadhyay","year":"2024","journal-title":"Expert. Rev. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/(SICI)1521-4141(199907)29:07<2319::AID-IMMU2319>3.0.CO;2-3","article-title":"Susceptibility or resistance to Leishmania infection is dictated by the macrophages evolved under the influence of IL-3 or GM-CSF","volume":"29","author":"Saha","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101516","DOI":"10.1016\/j.smim.2021.101516","article-title":"G-CSF\u2014A double edge sword in neutrophil mediated immunity","volume":"54","author":"Martin","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Christensen, S.B. (2022). Drugs that changed society: Microtubule-targeting agents belonging to taxanoids, macrolides and non-ribosomal peptides. Molecules, 27.","DOI":"10.3390\/molecules27175648"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1517\/14740338.6.5.609","article-title":"Paclitaxel: A review of adverse toxicities and novel delivery strategies","volume":"6","author":"Marupudi","year":"2007","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-025-02958-1","article-title":"Comparative efficacy and safety of cabazitaxel versus other taxanes: A systematic review and meta-analysis","volume":"14","author":"Abdu","year":"2025","journal-title":"Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.7150\/thno.92672","article-title":"IL4 receptor targeting enables nab-paclitaxel to enhance reprogramming of M2-type macrophages into M1-like phenotype via ROS-HMGB1-TLR4 axis and inhibition of tumor growth and metastasis","volume":"14","author":"Vadevoo","year":"2024","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1615\/CritRevImmunol.v32.i6.10","article-title":"M1 and M2 macrophages: Oracles of health and disease","volume":"32","author":"Mills","year":"2012","journal-title":"Crit. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dayakar, A., Chandrasekaran, S., Kuchipudi, S.V., and Kalangi, S.K. (2019). Cytokines: Key determinants of resistance or disease progression in visceral leishmaniasis: Opportunities for novel diagnostics and immunotherapy. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00670"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Vacas, A., Fern\u00e1ndez-Rubio, C., Larrea, E., Pe\u00f1a-Guerrero, J., and Nguewa, P.A. (2020). LmjF.22.0810 from Leishmania major modulates the Th2-Type immune response and is involved in leishmaniasis outcome. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110452"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Costa-da-Silva, A.C., Nascimento, D.O., Ferreira, J.R.M., Guimar\u00e3es-Pinto, K., Freire-de-Lima, L., Morrot, A., Decote-Ricardo, D., Filardy, A.A., and Freire-de-Lima, C.G. (2022). Immune responses in leishmaniasis: An overview. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7040054"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ayala, A., Llanes, A., Lleonart, R., and Restrepo, C.M. (2024). Advances in Leishmania vaccines: Current development and future prospects. Pathogens, 13.","DOI":"10.3390\/pathogens13090812"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00824-16","DOI":"10.1128\/IAI.00824-16","article-title":"Gamma interferon-regulated chemokines in Leishmania donovani infection in the liver","volume":"85","author":"Murray","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"155339","DOI":"10.1016\/j.cyto.2020.155339","article-title":"Chemokines in leishmaniasis: Map of cell movements highlights the landscape of infection and pathogenesis","volume":"147","author":"Pereira","year":"2021","journal-title":"Cytokine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.1128\/IAI.72.8.4918-4923.2004","article-title":"Involvement of the chemokine RANTES (CCL5) in resistance to experimental infection with Leishmania major","volume":"72","author":"Santiago","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molimm.2018.12.013","article-title":"Molecular variants of Leishmania (Viannia) braziliensis trigger distinct patterns of cytokines and chemokines expression in golden hamster","volume":"106","author":"Fradico","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Menezes-Souza, D., Guerra-S\u00e1, R., Carneiro, C.M., Carneiro, C.M., Vitoriano-Souza, J., Giunchetti, R.C., Teixeira-Carvalho, A., Silveira-Lemos, D., Oliveira, G.C., and Corr\u00eaa-Oliveira, R. (2012). Higher expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 chemokines in the skin associated with parasite density in canine visceral leishmaniasis. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001566"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.4049\/jimmunol.177.7.4636","article-title":"Inhibition of IL-2 induced IL-10 production as a principle of phase-specific immunotherapy","volume":"177","author":"Bodas","year":"2006","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Cabezas, B., Cec\u00edlio, P., Gaspar, T.B., G\u00e4rtner, F., Vasconcellos, R., and Cordeiro-da-Silva, A. (2019). Understanding resistance vs. susceptibility in visceral leishmaniasis using mouse models of Leishmania infantum infection. Front. Cell Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00030"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mul\u00e8, A., Crosato, V., Kuhns, D.B., Lorenzi, L., Chirico, C., Maifredi, G., Notarangelo, L.D., Castelli, F., and Tomasoni, L.R. (2024). Visceral leishmaniasis in immunocompetent hosts in Brescia: A case series and analysis of cytokine cascade. Microorganisms, 12.","DOI":"10.3390\/microorganisms12020394"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/eji.200324651","article-title":"Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha","volume":"34","author":"Rutella","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Suprien, C., Guimar\u00e3es, L.H., de Carvalho, L.P., and Machado, P.R.L. (2024). Pentavalent antimony associated with G-CSF in the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis. Pathogens, 13.","DOI":"10.3390\/pathogens13040301"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1172\/JCI117767","article-title":"Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis","volume":"95","author":"Murray","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1006\/cyto.2001.0935","article-title":"Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines","volume":"15","author":"Zaks","year":"2001","journal-title":"Cytokine"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Calvo-\u00c1lvarez, E., Stamatakis, K., Punz\u00f3n, C., \u00c1lvarez-Velilla, R., Tejer\u00eda, A., Escudero-Mart\u00ednez, J.M., P\u00e9rez-Pertejo, Y., Fresno, M., Bala\u00f1a-Fouce, R., and Reguera, R.M. (2015). Infrared fluorescent imaging as a potent tool for in vitro, ex vivo and in vivo models of visceral leishmaniasis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003666"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijpddr.2019.10.004","article-title":"Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB","volume":"11","author":"Reguera","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:47:43Z","timestamp":1774615663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073055"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073055","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}