RGD Reference Report - Interleukin-27 (IL-27) Mediates Susceptibility to Visceral Leishmaniasis by Suppressing the IL-17-Neutrophil Response. - Rat Genome Database

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

Authors: Quirino, Gustavo F S  Nascimento, Manuela S L  Davoli-Ferreira, Marcela  Sacramento, Lais A  Lima, Mikhael H F  Almeida, Roque P  Carregaro, Vanessa  Silva, João Santana 
Citation: Quirino GFS, etal., Infect Immun. 2016 Jul 21;84(8):2289-2298. doi: 10.1128/IAI.00283-16. Print 2016 Aug.
RGD ID: 126790520
Pubmed: PMID:27245409   (View Abstract at PubMed)
PMCID: PMC4962641   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.00283-16   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
visceral leishmaniasis  ISOIl27 (Mus musculus)126790520; 126790520mRNA more ...RGD 
visceral leishmaniasis  IEP 126790520mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)

Additional Information