IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-β Production Inhibits Fungal Clearance

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

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Candida spp. elicit cytokine production downstream of various pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs), Toll-like receptors (TLRs) and nucleotide oligomerisation domain (NOD)-like receptors (NLRs). IL-12 family members, IL-12p70 and IL-23, are important for host immunity against Candida spp. Herein we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to select Candida spp. We demonstrate a novel mechanism for C. parapsilosis-mediated induction of IL-27 in a TLR7-, MyD88- and NOD2-dependent manner. Our data revealed that IFN-beta is induced by C. parapsilosis, which in turn signals through the interferon-alpha/beta receptor (IFNAR) and STAT1/2 to induce IL-27. Moreover, IL 27R (WSX-1) deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared to WT mice. This was associated with increased levels of pro-inflammatory cytokines in the serum and increased IFN-gamma 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-beta 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.
Original languageEnglish
Pages (from-to)208-221
Number of pages14
JournalJournal of Immunology
Issue number1
Early online date3 Jun 2016
Publication statusPublished - Jul 2016

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