Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis.
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.
Conti
Heather R
HR
Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo, NY 14201, USA.
Shen
Fang
F
Nayyar
Namrata
N
Stocum
Eileen
E
Sun
Jianing N
JN
Lindemann
Matthew J
MJ
Ho
Allen W
AW
Hai
Justine Hoda
JH
Yu
Jeffrey J
JJ
Jung
Ji Won
JW
Filler
Scott G
SG
Masso-Welch
Patricia
P
Edgerton
Mira
M
Gaffen
Sarah L
SL
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
D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D000097043:Interleukin-22