The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22

J Immunol. 2012 Oct 1;189(7):3653-60. doi: 10.4049/jimmunol.1201797. Epub 2012 Aug 29.

Abstract

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspergillus fumigatus / immunology*
  • Cells, Cultured
  • Chronic Disease
  • Disease Models, Animal
  • Glucans / metabolism*
  • Interleukin-22
  • Interleukins / deficiency
  • Interleukins / genetics
  • Interleukins / physiology*
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / genetics
  • Lectins, C-Type / physiology*
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic / physiology*
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / microbiology
  • Respiratory Hypersensitivity / pathology*

Substances

  • Glucans
  • Interleukins
  • Lectins, C-Type
  • Receptors, Immunologic
  • beta-glucan receptor
  • dectin 1