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J Exp Med. 2014 Sep 22;211(10):2075-84. doi: 10.1084/jem.20130877. Epub 2014 Sep 8.

Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections.

Author information

1
Division of Rheumatology and Clinical Immunology, and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department of Immunology, and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261.
2
Department of Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224.
3
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
4
Department of Immunology, Genentech Inc., South San Francisco, CA 94080.
5
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852.
6
Division of Rheumatology and Clinical Immunology, and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department of Immunology, and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261 Division of Rheumatology and Clinical Immunology, and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department of Immunology, and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261.
7
Division of Rheumatology and Clinical Immunology, and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department of Immunology, and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261 Division of Rheumatology and Clinical Immunology, and Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department of Immunology, and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261 sig65@pitt.edu.

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.

PMID:
25200028
PMCID:
PMC4172215
DOI:
10.1084/jem.20130877
[Indexed for MEDLINE]
Free PMC Article

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