{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:15Z","timestamp":1785412515031,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P","award":["PTDC\/CVT-CVT\/0228\/2020"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P","award":["2023.11944.PEX"],"award-info":[{"award-number":["2023.11944.PEX"]}]},{"award":["PTDC\/CVT-CVT\/0228\/2020"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2023.11944.PEX"],"award-info":[{"award-number":["2023.11944.PEX"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Centre for Interdisciplinary Research in Animal Health","award":["UIDB\/00276\/2025"],"award-info":[{"award-number":["UIDB\/00276\/2025"]}]},{"name":"Global Health and Tropical Medicine","award":["UID\/04413\/2025"],"award-info":[{"award-number":["UID\/04413\/2025"]}]},{"name":"Associated Laboratory in Translation and Innovation Towards Global Health REAL","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Leishmaniasis caused by Leishmania infantum is a zoonotic disease endemic in many regions worldwide. The antigen-presenting dendritic cells (DCs) bridge the innate and adaptive immune response by activating T lymphocytes. Therefore, the present study examines whether T lymphocyte activation can be directed by autologous DCs primed by extracellular vesicles (EVs) derived from L. infantum. For this, lymphocytes were co-cultured with monocyte-derived DCs (moDCs) that were primed by EVs. moDC signaling and activation were examined by gene expression of toll-like receptors and cytokines. The antigen-presentation ability was analyzed through major histocompatibility complex molecules, and T cell subpopulations were explored by immunophenotyping. In co-cultures, EV-primed moDCs upregulated TLR2, TLR4, and TLR9, along with overexpression of MHC molecules. Co-cultures involving moDCs primed by EVs promoted the upregulation of both pro-inflammatory and regulatory cytokines associated with the expansion of non-conventional regulatory and central memory T cell subsets within the CD8+ T cell subpopulation. These findings suggest that activated moDCs can modulate cytotoxic lymphocytes, thereby promoting a balanced inflammatory microenvironment counterbalanced by a concurrent regulatory immune response. Thus, cell-based immune strategies using moDCs loaded with Leishmania-derived EVs represent a potential first step toward the development of innovative and personalized immune prophylactic and therapeutic approaches for leishmaniasis.<\/jats:p>","DOI":"10.3390\/cells15100919","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Autologous Dendritic Cells for T Cell Modulation: A Step Towards Personalized Medicine in Leishmaniasis"],"prefix":"10.3390","volume":"15","author":[{"given":"Mafalda","family":"Meunier","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Val\u00e9rio-Bolas","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-3879","authenticated-orcid":false,"given":"Armanda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Fr\u00f3is-Martins","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Banco de Sangue Animal (BSA), 4100-462 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Banco de Sangue Animal (BSA), 4100-462 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4514-5324","authenticated-orcid":false,"given":"Marta","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6639-1495","authenticated-orcid":false,"given":"Joana","family":"Palma-Marques","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-4717","authenticated-orcid":false,"given":"Manuela","family":"Carvalheiro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Telmo","family":"Nunes","sequence":"additional","affiliation":[{"name":"Microscopy Center, Faculty of Sciences of the University of Lisbon-FCUL-BioISI Ce3CE, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-2304","authenticated-orcid":false,"given":"Wilson T.","family":"Antunes","sequence":"additional","affiliation":[{"name":"Instituto Universit\u00e1rio Militar (IUM), Centro de Investiga\u00e7\u00e3o, Desenvolvimento e Inova\u00e7\u00e3o da Academia Militar (CINAMIL), Unidade Militar Laboratorial de Defesa Biol\u00f3gica e Qu\u00edmica (UMLDBQ), 1100-471 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-4679","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Alexandre-Pires","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-1224","authenticated-orcid":false,"given":"Isabel","family":"Pereira da Fonseca","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-3887","authenticated-orcid":false,"given":"Gabriela","family":"Santos-Gomes","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40249-020-0630-9","article-title":"Neglected tropical diseases: An effective global response to local poverty-related disease priorities","volume":"9","author":"Engels","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"ref_2","unstructured":"WHO (2025, December 07). Leishmaniasis (Who.Int). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hong, A., Zampieri, R.A., Shaw, J.J., Floeter-Winter, L.M., and Laranjeira-Silva, M.F. (2020). One Health approach to Leishmaniases: Understanding the disease dynamics through diagnostic tools. Pathogens, 9.","DOI":"10.3390\/pathogens9100809"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/tmi.13653","article-title":"Systematic Review: Re-emergence of human leishmaniasis in the Balkans","volume":"26","author":"Vaselek","year":"2021","journal-title":"Trop. Med. Int. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s11259-023-10171-5","article-title":"Is leishmaniasis the new emerging zoonosis in the world?","volume":"47","author":"Llobat","year":"2023","journal-title":"Vet. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100150","DOI":"10.1016\/j.crpvbd.2023.100150","article-title":"Knock, knock, knocking on Europe\u2019s door: Threat of leishmaniasis in Europe with a focus on Turkey","volume":"4","year":"2023","journal-title":"Curr. Res. Parasitol. Vector-Borne Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4269\/ajtmh.15-0408","article-title":"Social and Economic Burden of Human Leishmaniasis","volume":"94","author":"Okwor","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prevetmed.2017.11.022","article-title":"Risk profile for Leishmania infection in dogs coming from an area of visceral leishmaniasis reemergence","volume":"150","author":"Leal","year":"2018","journal-title":"Prev. Vet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Parker, L.A., Acosta, L., Gutierrez, M.N., Cruz, I., Nieto, J., Deschutter, E.J., and Bornay-Llinares, F.J. (2021). A novel sampling model to study the epidemiology of canine leishmaniasis in an urban environment. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.642287"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/intimm\/13.8.1053","article-title":"IL-1\u03b2 induces dendritic cells to produce IL-12","volume":"13","author":"Wesa","year":"2001","journal-title":"Int. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/cdd.2014.134","article-title":"New insights into IL-12-mediated tumor suppression","volume":"22","author":"Tugues","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1084\/jem.191.6.927","article-title":"The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli","volume":"191","author":"Inaba","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Szeto, C., Lobos, C.A., Nguyen, A.T., and Gras, S. (2020). TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010068"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tib\u00farcio, R., Nunes, S., Nunes, I., Ampuero, M.R., Silva, I.B., Lima, R., Tavares, N.M., and Brodskyn, C. (2019). Molecular aspects of dendritic cell activation in Leishmaniasis: An immunobiological view. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00227"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Volpedo, G., Pacheco-Fernandez, T., Bhattacharya, P., Oljuskin, T., Dey, R., Gannavaram, S., Satoskar, A.R., and Nakhasi, H.L. (2021). Determinants of innate immunity in Visceral Leishmaniasis and their implication in vaccine development. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.748325"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Van Den Eeckhout, B., Tavernier, J., and Gerlo, S. (2021). Interleukin-1 as innate mediator of T cell immunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.621931"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3176927","DOI":"10.1155\/jimr\/3176927","article-title":"Unveiling the interplay between dendritic cells and natural killer cells as key players in Leishmania infection","volume":"2025","author":"Meunier","year":"2025","journal-title":"J. Immunol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Margaroni, M., Agallou, M., Vasilakaki, A., Karagkouni, D., Skoufos, G., Hatzigeorgiou, A.G., and Karagouni, E. (2022). Transcriptional profiling of Leishmania infantum infected dendritic cells: Insights into the role of immunometabolism in host-parasite interaction. Microorganisms, 10.","DOI":"10.3390\/microorganisms10071271"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Doyle, L., and Wang, M. (2019). Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Val\u00e9rio-Bolas, A., Meunier, M., Palma-Marques, J., Rodrigues, A., Santos, A.M., Nunes, T., Ferreira, R., Armada, A., Alves, J.C., and Antunes, W. (2024). Exploiting Leishmania primed dendritic cells as potential immunomodulators of canine immune response. Cells, 13.","DOI":"10.3390\/cells13050445"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.4049\/jimmunol.1000541","article-title":"Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells","volume":"185","author":"Silverman","year":"2010","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s13071-018-2937-y","article-title":"Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes","volume":"11","author":"Marshall","year":"2018","journal-title":"Parasites Vectors"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0165-2427(97)00150-5","article-title":"A simple method for the simultaneous separation of peripheral blood mononuclear and polymorphonuclear cells in the dog","volume":"62","author":"Strasser","year":"1998","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Weber, J.I., Rodrigues, A.V., Val\u00e9rio-Bolas, A., Nunes, T., Carvalheiro, M., Antunes, W., Alexandre-Pires, G., da Fonseca, I.P., and Santos-Gomes, G. (2023). Insights on host\u2013parasite immunomodulation mediated by extracellular vesicles of cutaneous Leishmania shawi and Leishmania guyanensis. Cells, 12.","DOI":"10.3390\/cells12081101"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"de Freitas, B.E., Rodrigues, A., Palma-Marques, J., Weber, J.I., Val\u00e9rio-Bolas, A., Soares, R.P., Torrecilhas, A.C., Ferla, M., Baqui, M.M.A., and Cordova, R.A.G. (2025). Unleashing the immune modulatory potential of Leishmania amazonensis-derived extracellular vesicles in American cutaneous leishmaniasis. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1593363"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.rvsc.2020.02.004","article-title":"The balancing act: Immunology of leishmaniosis","volume":"130","author":"Toepp","year":"2020","journal-title":"Res. Vet. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.immuni.2006.08.003","article-title":"From vanilla to 28 flavors: Multiple varieties of T regulatory cells","volume":"25","author":"Shevach","year":"2006","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Schmitt, E.G., and Williams, C.B. (2013). Generation and function of induced regulatory T cells. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00152"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1073\/pnas.0408679102","article-title":"Foxp3+ CD25\u2212 CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion","volume":"102","author":"Zelenay","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","first-page":"7","article-title":"Comparative study of infectivity caused by promastigotes of Leishmania infantum MON-1, L. infantum MON-24 and L. donovani MON-18","volume":"43","author":"Abranches","year":"1996","journal-title":"Folia Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jim.2005.02.001","article-title":"Functional canine dendritic cells can be generated in vitro from peripheral blood mononuclear cells and contain a cytoplasmic ultrastructural marker","volume":"298","author":"Ibisch","year":"2005","journal-title":"J. Immunol. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"pdb.prot5080","DOI":"10.1101\/pdb.prot5080","article-title":"Bone marrow-derived macrophages (BMM): Isolation and applications","volume":"2008","author":"Weischenfeldt","year":"2008","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151935","DOI":"10.1016\/j.imbio.2020.151935","article-title":"M-CSF- and L929-derived macrophages present distinct metabolic profiles with similar inflammatory outcomes","volume":"225","author":"Davanzo","year":"2020","journal-title":"Immunobiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.cellimm.2007.01.005","article-title":"H-2 complex influences cytokine gene expression in Leishmania infantum-infected macrophages","volume":"243","author":"Rodrigues","year":"2006","journal-title":"Cell. Immunol."},{"key":"ref_35","unstructured":"Walker, R. (2025, October 16). All for One and One for All\u2014Fluorescence Minus One Controls. Available online: https:\/\/bitesizebio.com\/21127\/all-for-one-and-one-for-all-fluorescence-minus-one-controls\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.vetimm.2004.08.020","article-title":"Cytokine mRNA quantification in histologically normal canine duodenal mucosa by real-time RT-PCR","volume":"103","author":"Peters","year":"2005","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.domaniend.2005.04.006","article-title":"Cytokine expression in an ex vivo culture system of duodenal samples from dogs with chronic enteropathies: Modulation by probiotic bacteria","volume":"29","author":"Sauter","year":"2005","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.vetimm.2005.09.007","article-title":"Molecular cloning and tissue expression of canine Toll-like receptor 2 (TLR2)","volume":"110","author":"Ishii","year":"2006","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1189\/jlb.0408255","article-title":"CD5-low expression lymphocytes in canine peripheral blood show characteristics of natural killer cells","volume":"84","author":"Huang","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1292\/jvms.09-0590","article-title":"Ethyl pyruvate downregulates tumor necrosis factor alpha and interleukin (IL)-6 and upregulates IL-10 in lipopolysaccharide-stimulated canine peripheral blood mononuclear cells","volume":"72","author":"Yu","year":"2010","journal-title":"J. Vet. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Menezes-Souza, D., Guerra-S\u00e1, R., Carneiro, C.M., Vitoriano-Souza, J., Giunchetti, R.C., Teixeira-Carvalho, A., Silveira-Lemos, D., Oliveira, G.C., Corr\u00eaa -Oliveira, R., and Reis, A.B. (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_42","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.imbio.2016.08.009","article-title":"Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte","volume":"222","author":"Rodrigues","year":"2017","journal-title":"Immunobiology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Morales-Yuste, M., Mart\u00edn-S\u00e1nchez, J., and Corpas-Lopez, V. (2022). Canine Leishmaniasis: Update on epidemiology, diagnosis, treatment, and prevention. Vet. Sci., 9.","DOI":"10.3390\/vetsci9080387"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1002\/iub.2129","article-title":"Leishmania species-dependent functional duality of toll-like receptor 2","volume":"71","author":"Jafarzadeh","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood.2022016084","article-title":"IL-1\u03b2 expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function","volume":"140","author":"Li","year":"2022","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sacramento, L.A., Benevides, L., Maruyama, S.R., Tavares, L., Fukutani, K.F., Francozo, M., Sparwasser, T., Cunha, F.Q., Almeida, R.P., and da Silva, J.S. (2020). TLR4 abrogates the Th1 immune response through IRF1 and IFN-\u03b2 to prevent immunopathology during L. infantum infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008435"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/IAI.00975-15","article-title":"Toll-like receptor 9 signaling in dendritic cells regulates neutrophil recruitment to inflammatory foci following Leishmania infantum infection","volume":"83","author":"Sacramento","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1084\/jem.20061293","article-title":"NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs","volume":"204","author":"Schleicher","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Polari, L.P., Carneiro, P.P., Macedo, M., Machado, P.R.L., Scott, P., Carvalho, E.M., and Bacellar, O. (2019). Leishmania braziliensis infection enhances toll-like receptors 2 and 4 expression and triggers TNF-\u03b1 and IL-10 production in human cutaneous leishmaniasis. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00120"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00430-011-0202-5","article-title":"mTOR signaling pathway regulates the IL-12\/IL-10 axis in Leishmania donovani infection","volume":"201","author":"Cheekatla","year":"2012","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Santos, M.F., Alexandre-Pires, G., Pereira, M.A., Marques, C.S., Gomes, J., Correia, J., Duarte, A., Gomes, L., Rodrigues, A.V., and Basso, A. (2019). Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment. Front. Vet. Sci., 18.","DOI":"10.3389\/fvets.2019.00362"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"155266","DOI":"10.1016\/j.cyto.2020.155266","article-title":"Cytokines in the generation and function of regulatory T cell subsets in leishmaniasis","volume":"147","author":"Ghosh","year":"2021","journal-title":"Cytokine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jcpa.2011.03.001","article-title":"Cytokine gene expression in the tissues of dogs infected by Leishmania infantum","volume":"145","author":"Barbosa","year":"2011","journal-title":"J. Comp. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.4049\/jimmunol.176.12.7278","article-title":"IL-1\u03b2 breaks tolerance through expansion of CD25+ effector T cells","volume":"176","author":"Pai","year":"2006","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1084\/jem.20122006","article-title":"IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells","volume":"210","author":"Hogg","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1101\/sqb.2013.78.021246","article-title":"IL-1 strikingly enhances antigen-driven CD4 and CD8 T-cell responses","volume":"78","author":"Wang","year":"2013","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jdermsci.2007.03.002","article-title":"Tolerogenic dendritic cells and regulatory T cells: A two-way relationship","volume":"46","author":"Mahnke","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.imbio.2008.07.001","article-title":"Identification of regulatory T cells during experimental Leishmania infantum infection","volume":"214","author":"Rodrigues","year":"2009","journal-title":"Immunobiology"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Schwarz, T., Remer, K.A., Nahrendorf, W., Masic, A., Siewe, L., M\u00fcller, W., Roers, A., and Moll, H. (2013). T cell-derived IL-10 determines leishmaniasis disease outcome and is suppressed by a dendritic cell based vaccine. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003476"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"de Oliveira, B.C., da Silva, A.A., de Andrade Cavalcante, M.K., de Brito, M.E.F., de Castro, M.C.A.B., de Medeiros, V.L.S., de Freitas e Silva, R., and Pereira, V.R.A. (2023). Central and effector memory human CD4+ and CD8+ T cells during cutaneous leishmaniasis and after in vitro stimulation with Leishmania (Viannia) braziliensis epitopes. Vaccines, 11.","DOI":"10.3390\/vaccines11010158"},{"key":"ref_61","doi-asserted-by":"crossref","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."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/919\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:18:04Z","timestamp":1779697084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":61,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cells15100919"],"URL":"https:\/\/doi.org\/10.3390\/cells15100919","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}