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

Research output: Contribution to journalArticle

72 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

Fingerprint

Glucans
Hypersensitivity
Lung
Aspergillus fumigatus
Fungi
Fungal Spores
Interleukin-13
Interleukin-17
dectin 1
interleukin-22
Interleukin-1
Interleukin-4
Interleukin-10
Pneumonia
Asthma
T-Lymphocytes
Infection

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

Cite this

Lilly, L. M., Gessner, M. A., Dunaway, C. W., Metz, A. E., Schwiebert, L., Weaver, C. T., ... 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

The ß-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. / Lilly, Lauren M; Gessner, Melissa A; Dunaway, Chad W; Metz, Allison E; Schwiebert, Lisa; Weaver, Casey T; Brown, Gordon D; Steele, Chad.

In: The Journal of Immunology, Vol. 189, No. 7, 01.10.2012, p. 3653-3660.

Research output: Contribution to journalArticle

Lilly, LM, Gessner, MA, Dunaway, CW, Metz, AE, Schwiebert, L, Weaver, CT, Brown, GD & Steele, C 2012, 'The ß-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22', The Journal of Immunology, vol. 189, no. 7, pp. 3653-3660. https://doi.org/10.4049/jimmunol.1201797
Lilly LM, Gessner MA, Dunaway CW, Metz AE, Schwiebert L, Weaver CT et al. The ß-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. The Journal of Immunology. 2012 Oct 1;189(7):3653-3660. https://doi.org/10.4049/jimmunol.1201797
Lilly, Lauren M ; Gessner, Melissa A ; Dunaway, Chad W ; Metz, Allison E ; Schwiebert, Lisa ; Weaver, Casey T ; Brown, Gordon D ; Steele, Chad. / The ß-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. In: The Journal of Immunology. 2012 ; Vol. 189, No. 7. pp. 3653-3660.
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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-1{\ss} 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.",
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AB - 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.

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