Send to

Choose Destination
Infect Immun. 2016 Jul 21;84(8):2289-2298. doi: 10.1128/IAI.00283-16. Print 2016 Aug.

Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17-Neutrophil Response.

Author information

Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Biological and Health Science Center, Federal University of Sergipe, Aracaju, SE, Brazil.
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil


The relationship established between Leishmania infantum 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 L. infantum 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 L. infantum 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 in vivo, because Ebi3(-/-) mice can efficiently control parasite replication despite reduced levels of IFN-γ compared to wild-type mice. On the other hand, the absence of Ebi3 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 L. infantum infection. As a consequence of exacerbated IL-17A in Ebi3(-/-) 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 L. infantum infection and demonstrated its regulatory role in the IL-17A-neutrophil axis.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center