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: Agostinho Carvalho, Gloria Giovannini, Antonella De Luca, Carmen D'Angelo, Andrea Casagrande, Rossana G Iannitti, Giovanni Ricci, Cristina Cunha, Luigina Romani
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 9 Issue 3 Pg. 276-86 (May 2012) ISSN: 2042-0226 [Electronic] China
• PMID: 22543832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17
• Interleukins
• Lectins, C-Type
• Protein Isoforms
• dectin 1
• interleukin-22

Topics

• Adaptive Immunity
• Animals
• Candidiasis (immunology)
• Cells, Cultured
• Genetic Predisposition to Disease
• Immunity, Mucosal
• Immunologic Memory
• Interleukin-17 (metabolism)
• Interleukins (metabolism)
• Lectins, C-Type (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Protein Isoforms (genetics, metabolism)
• Signal Transduction
• T-Lymphocytes, Regulatory (immunology)
• Th1 Cells (immunology)
• Th17 Cells (immunology)