Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis
In: Journal of Experimental Medicine, vol 206, iss 2, 2009
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Zugriff:
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-alphabeta cells were more important than TCR-gammadelta 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 beta 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.
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Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis
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Autor/in / Beteiligte Person: | Conti, Heather R ; Shen, Fang ; Nayyar, Namrata ; Stocum, Eileen ; Sun, Jianing N ; Lindemann, Matthew J ; Ho, Allen W ; Hai, Justine Hoda ; Yu, Jeffrey J ; Jung, Ji Won ; Filler, Scott G ; Masso-Welch, Patricia ; Edgerton, Mira ; Gaffen, Sarah L |
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Zeitschrift: | Journal of Experimental Medicine, vol 206, iss 2, 2009 |
Veröffentlichung: | eScholarship, University of California, 2009 |
Medientyp: | academicJournal |
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