{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:54:20Z","timestamp":1789818860882,"version":"4.0.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The relationship established between<jats:named-content content-type=\"genus-species\">Leishmania infantum<\/jats:named-content>and the vertebrate host can lead to a self-healing infection or to the manifestation of visceral leishmaniasis, a chronic systemic infection associated with high rates of mortality. We hypothesized that regulatory cytokines, such as interleukin-27 (IL-27), play a role in susceptibility to<jats:named-content content-type=\"genus-species\">L. infantum<\/jats:named-content>infection. IL-27 is a heterodimeric cytokine composed of IL-27p28 and EBi3 subunits which, when combined, bind to IL-27R, leading to STAT-1 and -3 activation, playing a role in the regulation of the immune response. We observed in this work that IL-27 regulates the Th1\/Th17 profiles in a mouse model of visceral leishmaniasis (VL) caused by<jats:named-content content-type=\"genus-species\">L. infantum<\/jats:named-content>. We showed here that the pathogen recognition by endosomal Toll-like receptors triggers a type I interferon (IFN) response, which acts through the type I IFN receptor and interferon regulatory factor 1 to induce IL-27 production by macrophages. Furthermore, IL-27 plays a major regulatory role<jats:italic>in vivo<\/jats:italic>, because<jats:italic>Ebi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice can efficiently control parasite replication despite reduced levels of IFN-\u03b3 compared to wild-type mice. On the other hand, the absence of<jats:italic>Ebi3<\/jats:italic>leads to exacerbated IL-17A production in the infected organs as well as in a coculture system, suggesting a direct regulatory action of IL-27 during<jats:named-content content-type=\"genus-species\">L. infantum<\/jats:named-content>infection. As a consequence of exacerbated IL-17A in<jats:italic>Ebi3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, a greater neutrophil influx was observed in the target organs, playing a role in parasite control. Thus, this work unveiled the molecular steps of IL-27 production after<jats:named-content content-type=\"genus-species\">L. infantum<\/jats:named-content>infection and demonstrated its regulatory role in the IL-17A\u2013neutrophil axis.<\/jats:p>","DOI":"10.1128\/iai.00283-16","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T03:18:46Z","timestamp":1464751126000},"page":"2289-2298","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17\u2013Neutrophil Response"],"prefix":"10.1128","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3995-6259","authenticated-orcid":false,"given":"Gustavo F. 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L.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Davoli-Ferreira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais A.","family":"Sacramento","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhael H. 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