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

Patin, Emmanuel, Jones, Adam V., Thompson, Aiysha, Clement, Mathew, Liao, Chia-Te, Griffiths, James S., Wallace, Leah, Bryant, Clare E., Lang, Roland, Rosenstiel, Philip, Humphreys, Ian R., Taylor, Philip Russel, Jones, Gareth Wyn and Orr, Selinda Jane 2016. IL-27 induced by Select Candida spp. via TLR7/NOD2 signaling and IFN-β production inhibits fungal clearance. The Journal of Immunology 197 (1) , pp. 208-221. 10.4049/​jimmunol.1501204

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Abstract

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-β is induced by C. parapsilosis, which in turn signals through the interferon-α/β 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-γ 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Funders: Wellcome Trust
Date of First Compliant Deposit: 25 May 2016
Date of Acceptance: 27 April 2016
Last Modified: 24 May 2019 20:30
URI: http://orca.cf.ac.uk/id/eprint/91237

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