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¹ Department of Oral Biology, School of Dental Medicine; ² Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences; ³ Department of Biotechnology, University at Buffalo, State University of New York, Buffalo, NY 14201
⁴ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095
⁵ University of Pittsburgh Department of Medicine, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA 15261

CORRESPONDENCE Sarah L. Gaffen: sig65{at}pitt.edu

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19^–/–) and IL-17R–deficient (IL-17RA^–/–) mice experienced severe OPC, whereas Th1-deficient (IL-12p35^–/–) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19^–/– and IL-17RA^–/–, but not IL-12^–/–, mice, and TCR-β cells were more important than TCR- cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and β defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.

© 2009 Conti et al.
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