title: Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections.
abstract: Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1-/- mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4-CD8- cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hernández-Santos
authors.forename: A R
authors.initials: AR
authors.lastname: Huppler
authors.forename: A C
authors.initials: AC
authors.lastname: Peterson
authors.forename: S A
authors.initials: SA
authors.lastname: Khader
authors.forename: K C
authors.initials: KC
authors.lastname: McKenna
authors.forename: S L
authors.initials: SL
authors.lastname: Gaffen
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000276:immunology*; D009960:Oropharynx / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D058504:Th17 Cells / Q000276:immunology* / Q000637:transplantation
chemical_list: D020381:Interleukin-17