title: Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis.
abstract: The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
authors.forename: Agostinho
authors.initials: A
authors.lastname: Carvalho
authors.forename: Gloria
authors.initials: G
authors.lastname: Giovannini
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Angelo
authors.forename: Andrea
authors.initials: A
authors.lastname: Casagrande
authors.forename: Rossana G
authors.initials: RG
authors.lastname: Iannitti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricci
authors.forename: Cristina
authors.initials: C
authors.lastname: Cunha
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D000097043:Interleukin-22; D000099181:Dectin-1
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D037181:Lectins, C-Type; D020033:Protein Isoforms; D000097043:Interleukin-22; D000099181:Dectin-1