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

Research output: Contribution to journalArticle

75 Citations (Scopus)

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

Fingerprint

Aspergillus fumigatus
Lung
Interleukin-23
Interleukin-17
dectin 1
interleukin-22
Interleukin-18
Neutrophil Infiltration
Bronchoalveolar Lavage Fluid
Interleukin-1
Interleukin-6

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

Cite this

Gessner, M. A., Werner, J. L., Lilly, L. M., Nelson, M. P., Metz, A. E., Dunaway, C. W., ... 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

Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. / Gessner, Melissa A; Werner, Jessica L; Lilly, Lauren M; Nelson, Michael P; Metz, Allison E; Dunaway, Chad W; Chan, Yvonne R; Ouyang, Wenjun; Brown, Gordon D; Weaver, Casey T; Steele, Chad.

In: Infection and Immunity, Vol. 80, No. 1, 01.2012, p. 410-417.

Research output: Contribution to journalArticle

Gessner, MA, Werner, JL, Lilly, LM, Nelson, MP, Metz, AE, Dunaway, CW, Chan, YR, Ouyang, W, Brown, GD, Weaver, CT & Steele, C 2012, 'Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus', Infection and Immunity, vol. 80, no. 1, pp. 410-417. https://doi.org/10.1128/IAI.05939-11
Gessner, Melissa A ; Werner, Jessica L ; Lilly, Lauren M ; Nelson, Michael P ; Metz, Allison E ; Dunaway, Chad W ; Chan, Yvonne R ; Ouyang, Wenjun ; Brown, Gordon D ; Weaver, Casey T ; Steele, Chad. / Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. In: Infection and Immunity. 2012 ; Vol. 80, No. 1. pp. 410-417.
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AU - Metz, Allison E

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AB - 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.

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KW - cells, cultured

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KW - lectins, C-type

KW - lung

KW - mice

KW - mice, inbred C57BL

KW - mice, knockout

KW - neutrophils

KW - pulmonary aspergillosis

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