Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

The recognition of b-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses.Here,wereportthatthefunctionalactivityofdectin-1inmucosalimmunitytoCandidaalbicansisinfluencedbythegenetic 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 adaptiveTh1responses.Incontrast,theresistanceofdectin-1-deficientBALB/cmicewasassociatedwithincreasedIL-17AandIL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/ noncanonical NF-kB 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. Cellular & Molecular Immunology (2012) 9, 276–286; doi:10.1038/cmi.2012.1; published online 30 April 2012