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Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections. J Exp Med 2014 Sep 22;211(10):2075-84

Date

09/10/2014

Pubmed ID

25200028

Pubmed Central ID

PMC4172215

DOI

10.1084/jem.20130877

Scopus ID

2-s2.0-84907202739 (requires institutional sign-in at Scopus site)   236 Citations

Abstract

Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of γδ T cells and CD3(+)CD4(+)CD44(hi)TCRβ(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β(-/-) and TCR-δ(-/-) mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1(-/-), IL-7Rα(-/-), and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens.

Author List

Conti HR, Peterson AC, Brane L, Huppler AR, Hernández-Santos N, Whibley N, Garg AV, Simpson-Abelson MR, Gibson GA, Mamo AJ, Osborne LC, Bishu S, Ghilardi N, Siebenlist U, Watkins SC, Artis D, McGeachy MJ, Gaffen SL

Author

Anna Huppler MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Candida albicans
Candidiasis
Flow Cytometry
Immunity, Innate
Interleukin-23
Mice
Mice, Knockout
Microscopy, Confocal
Mouth
Real-Time Polymerase Chain Reaction
Receptors, Antigen, T-Cell, gamma-delta
Receptors, Interleukin-17
Th17 Cells