Requisite role for the dectin-1 β-glucan receptor in pulmonary defense against Aspergillus fumigatus

Jessica L Werner, Allison E Metz, Dawn Horn, Trenton R Schoeb, Matthew M Hewitt, Lisa M Schwiebert, Ines Faro-Trindade, Gordon D Brown, Chad Steele

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293 Citations (Scopus)

Abstract

Immune suppression increases the incidence of invasive fungal infections, particularly those caused by the opportunistic mold Aspergillus fumigatus. Previous investigations revealed that members of the TLR family are not absolutely required for host defense against A. fumigatus in nonimmunosuppressed hosts, suggesting that other pattern recognition receptors are involved. We show in this study that naive mice (i.e., not pharmacologically immunosuppressed) lacking the beta-glucan receptor Dectin-1 (Dectin-1(-/-)) are more sensitive to intratracheal challenge with A. fumigatus than control mice, exhibiting >80% mortality within 5 days, ultimately attributed to a compromise in respiratory mechanics. In response to A. fumigatus challenge, Dectin-1(-/-) mice demonstrated impaired IL-1alpha, IL-1beta, TNF-alpha, CCL3/MIP-1alpha, CCL4/MIP-1beta, and CXCL1/KC production, which resulted in insufficient lung neutrophil recruitment and uncontrolled A. fumigatus lung growth. Alveolar macrophages from Dectin-1(-/-) mice failed to produce proinflammatory mediators in response to A. fumigatus, whereas neutrophils from Dectin-1(-/-) mice had impaired reactive oxygen species production and impaired killing of A. fumigatus. We further show that IL-17 production in the lung after A. fumigatus challenge was Dectin-1 dependent, and that neutralization of IL-17 significantly impaired A. fumigatus clearance. Collectively, these results support a requisite role for Dectin-1 in in vivo defense against A. fumigatus.
Original languageEnglish
Pages (from-to)4938-4946
Number of pages9
JournalThe Journal of Immunology
Volume182
Issue number8
DOIs
Publication statusPublished - 15 Apr 2009

Keywords

  • animals
  • aspergillosis
  • Aspergillus fumigatus
  • disease susceptibility
  • interleukin-17
  • lung diseases, fungal
  • male
  • membrane proteins
  • mice
  • nerve tissue proteins
  • neutrophils
  • receptors, immunologic
  • survival rate
  • time factors

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  • Cite this

    Werner, J. L., Metz, A. E., Horn, D., Schoeb, T. R., Hewitt, M. M., Schwiebert, L. M., Faro-Trindade, I., Brown, G. D., & Steele, C. (2009). Requisite role for the dectin-1 β-glucan receptor in pulmonary defense against Aspergillus fumigatus. The Journal of Immunology, 182(8), 4938-4946. https://doi.org/10.4049/jimmunol.0804250