title: Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis.
abstract: 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.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo, NY 14201, USA.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Conti
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.forename: Namrata
authors.initials: N
authors.lastname: Nayyar
authors.forename: Eileen
authors.initials: E
authors.lastname: Stocum
authors.forename: Jianing N
authors.initials: JN
authors.lastname: Sun
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lindemann
authors.forename: Allen W
authors.initials: AW
authors.lastname: Ho
authors.forename: Justine Hoda
authors.initials: JH
authors.lastname: Hai
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Yu
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Jung
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Patricia
authors.initials: P
authors.lastname: Masso-Welch
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002180:Candidiasis, Oral / Q000209:etiology* / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097043:Interleukin-22
chemical_list: D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D000097043:Interleukin-22