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

Lauren M Lilly, Melissa A Gessner, Chad W Dunaway, Allison E Metz, Lisa Schwiebert, Casey T Weaver, Gordon D Brown, Chad Steele

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81 Citations (Scopus)

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 ß-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, ß-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1ß 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-ß levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-¿, 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 ß-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.
Original languageEnglish
Pages (from-to)3653-3660
Number of pages8
JournalThe Journal of Immunology
Volume189
Issue number7
Early online date29 Aug 2012
DOIs
Publication statusPublished - 1 Oct 2012

Keywords

  • animals
  • interleukins
  • disease models, animal
  • mice
  • glucans
  • mice, knockout
  • mice, 129 strain
  • lectins, C-type
  • receptors, immunologic
  • cells, cultured
  • lung
  • Aspergillus fumigatus
  • mice, inbred C57BL
  • chronic disease
  • respiratory hypersensitivity

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  • Cite this

    Lilly, L. M., Gessner, M. A., Dunaway, C. W., Metz, A. E., Schwiebert, L., Weaver, C. T., Brown, G. D., & Steele, C. (2012). The ß-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. The Journal of Immunology, 189(7), 3653-3660. https://doi.org/10.4049/jimmunol.1201797