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

• Published in: Cellular & molecular immunology 2012-05, Vol.9 (3), p.276-286
• Main Authors: Carvalho, Agostinho, Giovannini, Gloria, De Luca, Antonella, D'Angelo, Carmen, Casagrande, Andrea, Iannitti, Rossana G, Ricci, Giovanni, Cunha, Cristina, Romani, Luigina
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Animals; Antibodies; beta -Glucan; Biomedical and Life Sciences; Biomedicine; Candida albicans; Candidiasis; Candidiasis - immunology; Cell activation; Cells, Cultured; Cytokines; 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 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; Th17 Cells - immunology; Vaccine; Vagina
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2012.1

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.