IL-27 induced by select candida spp. via TLR7/NOD2 signaling and IFN-β production inhibits fungal clearance

Emmanuel C. Patin, Adam V. Jones, Aiysha Thompson, Mathew Clement, Chia Te Liao, James S. Griffiths, Leah E. Wallace, Clare E. Bryant, Roland Lang, Philip Rosenstiel, Ian R. Humphreys, Philip R. Taylor, Gareth W. Jones, Selinda J. Orr

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26 引文 斯高帕斯(Scopus)

摘要

Candida spp. elicit cytokine production downstream of various pathogen recognition receptors, including C-type lectin-like receptors, TLRs, and nucleotide oligomerization domain (NOD)-like receptors. IL-12 family members IL-12p70 and IL-23 are important for host immunity against Candida spp. In this article, we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to selected Candida spp. We demonstrate a novel mechanism for Candida parapsilosis-mediated induction of IL-27 in a TLR7-, MyD88-, and NOD2-dependent manner. Our data revealed that IFN-β is induced by C. parapsilosis, which in turn signals through the IFN-α/β receptor and STAT1/2 to induce IL-27. Moreover, IL-27R (WSX-1)-deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared with wild-type mice. This was associated with increased levels of proinflammatory cytokines in the serum and increased IFN-g and IL-17 responses in the spleens of IL-27R-deficient mice. Thus, our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-β, and IL-27, and we have identified an important role for IL-27 in the immune response against C. parapsilosis. Overall, these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens.

原文英語
頁(從 - 到)208-221
頁數14
期刊Journal of Immunology
197
發行號1
DOIs
出版狀態已發佈 - 七月 1 2016
對外發佈

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學

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