{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:27:58Z","timestamp":1775762878214,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"],"award-info":[{"award-number":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["CIISA, UIDB\/00276\/2020"],"award-info":[{"award-number":["CIISA, UIDB\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["GHTM, UID\/04413\/2020"],"award-info":[{"award-number":["GHTM, UID\/04413\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT\u2014Foundation for Science and Technology","doi-asserted-by":"publisher","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"],"award-info":[{"award-number":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["CIISA, UIDB\/00276\/2020"],"award-info":[{"award-number":["CIISA, UIDB\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["GHTM, UID\/04413\/2020"],"award-info":[{"award-number":["GHTM, UID\/04413\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal","doi-asserted-by":"publisher","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Al4AnimalS","award":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"],"award-info":[{"award-number":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"]}]},{"name":"Al4AnimalS","award":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"]}]},{"name":"Al4AnimalS","award":["CIISA, UIDB\/00276\/2020"],"award-info":[{"award-number":["CIISA, UIDB\/00276\/2020"]}]},{"name":"Al4AnimalS","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"Al4AnimalS","award":["GHTM, UID\/04413\/2020"],"award-info":[{"award-number":["GHTM, UID\/04413\/2020"]}]},{"name":"Al4AnimalS","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}]},{"name":"Global Health and Tropical Medicine","award":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"],"award-info":[{"award-number":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"]}]},{"name":"Global Health and Tropical Medicine","award":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"]}]},{"name":"Global Health and Tropical Medicine","award":["CIISA, UIDB\/00276\/2020"],"award-info":[{"award-number":["CIISA, UIDB\/00276\/2020"]}]},{"name":"Global Health and Tropical Medicine","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"Global Health and Tropical Medicine","award":["GHTM, UID\/04413\/2020"],"award-info":[{"award-number":["GHTM, UID\/04413\/2020"]}]},{"name":"Global Health and Tropical Medicine","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}]},{"name":"LA-REAL","award":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"],"award-info":[{"award-number":["EXPL\/CVT-CVT\/0175\/2021 (DOI 10.54499\/EXPL\/CVT-CVT\/0175\/2021)"]}]},{"name":"LA-REAL","award":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/0228\/2020 (DOI 10.54499\/PTDC\/CVT-CVT\/0228\/2020)"]}]},{"name":"LA-REAL","award":["CIISA, UIDB\/00276\/2020"],"award-info":[{"award-number":["CIISA, UIDB\/00276\/2020"]}]},{"name":"LA-REAL","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"LA-REAL","award":["GHTM, UID\/04413\/2020"],"award-info":[{"award-number":["GHTM, UID\/04413\/2020"]}]},{"name":"LA-REAL","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human zoonotic visceral leishmaniasis (ZVL) and canine leishmaniasis (CanL) constitute a major public and veterinary health concern and are both caused by the infection with the protozoan parasite Leishmania infantum. One of the main target organs in CanL is the liver. This complex organ, composed of various highly specialized cell types, has garnered significant attention from the scientific community as a crucial player in innate immune functions. In the context of CanL, liver infection by parasites and the host immune response generated strongly influence the disease outcome. Thus, taking advantage of a co-culture system involving canine hepatocytes and L. infantum-infected autologous Kupffer cells (KCs), allowing cell-to-cell interaction, the current report aims to shed light on the hepatocyte-KCs immune interaction. The co-culture of infected KCs with hepatocytes revealed a vital role of these cells in the activation of a local immune response against L. infantum parasites. Although KCs alone can be immunologically silenced by L. infantum infection, the cell-to-cell interaction with hepatocytes in co-culture can lead to local immune activation. In co-culture it was observed gene expression increased the number of innate immune receptors, specifically cell membrane TLR2 and cytoplasmatic NOD1 along with high TNF-\u03b1 generation. Altogether, these results suggest that the immune response generated in co-culture could induce the recruitment of other circulating cells to contain and contribute to the resolution of the infection in the liver. This work also enhances our understanding of the liver as a vital organ in innate immunity within the context of CanL.<\/jats:p>","DOI":"10.3390\/microorganisms12091887","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T06:39:16Z","timestamp":1726209556000},"page":"1887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Kupffer Cells and Hepatocytes: A Key Relation in the Context of Canine Leishmaniasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-3879","authenticated-orcid":false,"given":"Armanda","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-4679","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Alexandre-Pires","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Avenida da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1200-771 Lisbon, Portugal"}]},{"given":"Ana","family":"Val\u00e9rio-Bolas","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal"}]},{"given":"Telmo","family":"Nunes","sequence":"additional","affiliation":[{"name":"Microscopy Center, Faculty of Sciences, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-1224","authenticated-orcid":false,"given":"Isabel","family":"Pereira da Fonseca","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Avenida da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1200-771 Lisbon, Portugal"}]},{"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), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alvar, J., V\u00e9lez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., den Boer, M., and WHO Leishmaniasis Control Team (2012). Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_2","first-page":"100971","article-title":"A climatic suitability indicator to support Leishmania infantum surveillance in Europe: A modelling study","volume":"43","author":"Carvalho","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/1756-3305-4-197","article-title":"One Health: The global challenge of epidemic and endemic leishmaniasis","volume":"4","author":"Day","year":"2011","journal-title":"Parasites Vectors"},{"key":"ref_4","unstructured":"(2024, September 06). TDR|Neglected Tropical Disease (NTD) Research. Visceral Leishmaniasis Research. Available online: https:\/\/tdr.who.int\/our-work\/research-for-implementation\/neglected-tropical-diseases-research\/visceral-leishmaniasis-research."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vilas-Boas, D.F., Nakasone, E.K.N., Gon\u00e7alves, A.A.M., Lair, D.F., Oliveira, D.S.d., Pereira, D.F.S., Silva, G.G., Conrado, I.d.S.S., Resende, L.A., and Zald\u00edvar, M.F. (2024). Global Distribution of Canine Visceral Leishmaniasis and the Role of the Dog in the Epidemiology of the Disease. Pathogens, 13.","DOI":"10.3390\/pathogens13060455"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s10584-021-03300-z","article-title":"Climate change impacts on infectious diseases in the Eastern Mediterranean and the Middle East (EMME)\u2014Risks and recommendations","volume":"169","author":"Paz","year":"2021","journal-title":"Clim. Chang."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101088","DOI":"10.1016\/j.nmni.2023.101088","article-title":"Climate change and future infectious diseases: A growing threat","volume":"52","author":"Arikan","year":"2023","journal-title":"New Microbes New Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.vetimm.2010.06.007","article-title":"Canine leishmaniasis. Immunophenotypic profile of leukocytes in different compartments of symptomatic, asymptomatic and treated dogs","volume":"137","author":"Martins","year":"2010","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"618","DOI":"10.4269\/ajtmh.2004.70.618","article-title":"Organ-specific immunity in canine visceral leishmaniasis: Analysis of symptomatic and asymptomatic dogs naturally infected with Leishmania chagasi","volume":"70","author":"Diaz","year":"2004","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/cmi.2016.09","article-title":"Basic liver immunology","volume":"13","author":"Gao","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/cmi.2015.97","article-title":"Hepatocytes: A key cell type for innate immunity","volume":"13","author":"Zhou","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gong, J., Tu, W., Liu, J., and Tian, D. (2022). Hepatocytes: A key role in liver inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1083780"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ni.2691","article-title":"Immune surveillance by the liver","volume":"14","author":"Jenne","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Musrati, M.A., De Baetselier, P., Movahedi, K., and Van Ginderachter, J.A. (2023). Ontogeny, functions and reprogramming of Kupffer cells upon infectious disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1238452"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cimid.2017.09.004","article-title":"Leishmania infantum exerts immunomodulation in canine Kupffer cells reverted by meglumine antimoniate","volume":"55","author":"Rodrigues","year":"2017","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1017\/S0031182018002068","article-title":"Dog hepatocytes are key effector cells in the liver innate immune response to Leishmania infantum","volume":"146","author":"Rodrigues","year":"2019","journal-title":"Parasitology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.V., Alexandre-Pires, G., Val\u00e9rio-Bolas, A., Santos-Mateus, D., Rafael-Fernandes, M., Pereira, M.A., Ligeiro, D., Nunes, T., Alves-Azevedo, R., and Santos, M. (2020). 3D-Hepatocyte Culture Applied to Parasitology: Immune Activation of Canine Hepatic Spheroids Exposed to Leishmania Infantum. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120628"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.V., Val\u00e9rio-Bolas, A., Alexandre-Pires, G., Aires-Pereira, M., Nunes, T., Ligeiro, D., Pereira da Fonseca, I., and Santos-Gomes, G. (2022). Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites. Biology, 11.","DOI":"10.3390\/biology11010100"},{"key":"ref_19","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_20","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_21","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.intimp.2011.04.023","article-title":"Toll-like receptors in acute liver injury and regeneration","volume":"11","author":"Chen","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/liv.12315","article-title":"Toll-like receptors and liver disease","volume":"34","author":"Kesar","year":"2014","journal-title":"Liver Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: Time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000Prime Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.22034","article-title":"Liver: An organ with predominant innate immunity","volume":"47","author":"Gao","year":"2008","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nakamoto, N., and Kanai, T. (2014). Role of Toll-like receptors in immune activation and tolerance in the liver. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00221"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.4254\/wjh.v8.i32.1354","article-title":"Toll-like receptors in pathophysiology of liver diseases","volume":"8","author":"Kiziltas","year":"2016","journal-title":"World J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2613.2001.00199.x","article-title":"Tissue granuloma structure-function in experimental visceral leishmaniasis","volume":"82","author":"Murray","year":"2001","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00281-015-0548-7","article-title":"Lessons from other diseases: Granulomatous inflammation in leishmaniasis","volume":"38","author":"Kaye","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fischer, L., Lucendo-villarin, B., Hay, D.C., and O\u2019farrelly, C. (2020). Human PSC-Derived Hepatocytes Express Low Levels of Viral Pathogen Recognition Receptors, but Are Capable of Mounting an Effective Innate Immune Response. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113831"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1172\/JCI27083","article-title":"Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis","volume":"116","author":"Anand","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.cytox.2020.100043","article-title":"Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility to Leishmania infection","volume":"2","author":"Osero","year":"2020","journal-title":"Cytokine X"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1172\/JCI23215","article-title":"IL-10\u2013producing and naturally occurring CD4+ Tregs: Limiting collateral damage","volume":"114","author":"Vieira","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.3748\/wjg.v12.i11.1681","article-title":"Interleukin-10 and chronic liver disease","volume":"12","author":"Zhang","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111341","DOI":"10.1016\/j.intimp.2023.111341","article-title":"Interleukin-10 gene intervention ameliorates liver fibrosis by enhancing the immune function of natural killer cells in liver tissue","volume":"127","author":"Chen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137823","DOI":"10.1155\/2015\/137823","article-title":"Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture Healing Biology and Potential Clinical Applications","volume":"2015","author":"Poniatowski","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0008-8749(92)90142-C","article-title":"Interleukin-4 fails to inhibit interferon-\u03b3-induced activation of human colostral macrophages","volume":"141","author":"Lehn","year":"1992","journal-title":"Cell. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/infdis\/165.2.344","article-title":"Interleukin-4 Inhibits Human Macrophage Activation by Tumor Necrosis Factor, Granulocyte-Monocyte Colony-Stimulating Factor, and Interleukin-3 for Antileishmanial Activity and Oxidative Burst Capacity","volume":"165","author":"Ho","year":"1992","journal-title":"J. Infect. Dis."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/9\/1887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:55:34Z","timestamp":1760111734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/9\/1887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,13]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["microorganisms12091887"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12091887","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,13]]}}}