Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus

Melissa A Gessner, Jessica L Werner, Lauren M Lilly, Michael P Nelson, Allison E Metz, Chad W Dunaway, Yvonne R Chan, Wenjun Ouyang, Gordon D Brown, Casey T Weaver, Chad Steele

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Abstract

We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense against A. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early after A. fumigatus challenge. Culturing cells from enzymatic lung digests ex vivo further demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1ß, IL-6, or IL-18 but required IL-23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1-deficient mice. In vivo neutralization of IL-22 in the lungs of WT mice resulted in impaired A. fumigatus lung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden after A. fumigatus challenge in the presence of impaired IL-1a, tumor necrosis factor alpha (TNF-a), CCL3/MIP-1a, and CCL4/MIP-1ß production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from both A. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity against A. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impaired A. fumigatus clearance. Moreover, lung S100a8, S100a9, and Reg3g mRNA expression was not lower in either Dectin-1-deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense against A. fumigatus is mediated by Dectin-1-dependent IL-22 production.
Original languageEnglish
Pages (from-to)410-417
Number of pages8
JournalInfection and Immunity
Volume80
Issue number1
Early online date28 Oct 2011
DOIs
Publication statusPublished - Jan 2012

Keywords

  • animals
  • Aspergillus fumigatus
  • bronchoalveolar lavage fluid
  • cells, cultured
  • colony count, microbial
  • interleukins
  • lectins, C-type
  • lung
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • neutrophils
  • pulmonary aspergillosis

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    Gessner, M. A., Werner, J. L., Lilly, L. M., Nelson, M. P., Metz, A. E., Dunaway, C. W., Chan, Y. R., Ouyang, W., Brown, G. D., Weaver, C. T., & Steele, C. (2012). Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. Infection and Immunity, 80(1), 410-417. https://doi.org/10.1128/IAI.05939-11