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

Cell Mol Immunol. 2012 May;9(3):276-86. doi: 10.1038/cmi.2012.1. Epub 2012 Apr 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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