Journal Article

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

Casagrande, Andrea, Iannitti, Rossana G, Romani, Luigina, Giovannini, Gloria, D'Angelo, Carmen, Ricci, Giovanni, Cunha, Cristina, De Luca, Antonella, Carvalho, Agostinho

2012

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adaptive Immunity / Animals / Antibodies / beta -Glucan / Biomedical and Life Sciences / Biomedicine / Candida albicans / Candidiasis / Candidiasis - immunology / Cell activation / Cells, Cultured / Cytokines / genetic background / Genetic Predisposition to Disease / Glucans / Helper cells / Hydrocarbons / Immune response / Immunity, Mucosal / Immunologic Memory / Immunological memory / Immunology / Infection / Interleukin 22 / Interleukin-17 - metabolism / Interleukins - metabolism / Isoforms / Lectins, C-Type - genetics / Lectins, C-Type - metabolism / Lymphocytes T / Medical Microbiology / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Microbiology / Mucosal candidiasis / Mucosal immunity / NF- Kappa B protein / NF-κB protein / Protein Isoforms - genetics / Protein Isoforms - metabolism / research-article / Signal Transduction / T-Lymphocytes, Regulatory - immunology / Th1 Cells - immunology / Th1/Th17 / Th17 Cells - immunology / Vaccine / Vagina