Complement component 3C3 and C3a receptor are required in chitin-dependent allergic sensitization to Aspergillus fumigatus but dispensable in chitin-induced innate allergic inflammation

René M. Roy, Hugo C. Paes, Som G. Nanjappa, Ron Sorkness, David Gasper, Alana Sterkel, Marcel Wüthrich, Bruce S. Kleina

Research output: Contribution to journalArticle

Abstract

Levels of the anaphylatoxin C3a are increased in patients with asthma compared with those in nonasthmatics and increase further still during asthma exacerbations. However, the role of C3a during sensitization to allergen is poorly understood. Sensitization to fungal allergens, such as Aspergillus fumigatus, is a strong risk factor for the development of asthma. Exposure to chitin, a structural polysaccharide of the fungal cell wall, induces innate allergic inflammation and may promote sensitization to fungal allergens. Here, we found that coincubation of chitin with serum or intratracheal administration of chitin in mice resulted in the generation of C3a. We established a model of chitin-dependent sensitization to soluble Aspergillus antigens to test the contribution of complement to these events. C3-/- and C3aR-/- mice were protected from chitin-dependent sensitization to Aspergillus and had reduced lung eosinophilia and type 2 cytokines and serum IgE. In contrast, complement-deficient mice were not protected against chitin-induced innate allergic inflammation. In sensitized mice, plasmacytoid dendritic cells from complement-deficient animals acquired a tolerogenic profile associated with enhanced regulatory T cell responses and suppressed Th2 and Th17 responses specific for Aspergillus. Thus, chitin induces the generation of C3a in the lung, and chitindependent allergic sensitization to Aspergillus requires C3aR signaling, which suppresses regulatory dendritic cells and T cells and induces allergy-promoting T cells.

Original languageEnglish (US)
Article numbere00162-13
JournalmBio
Volume4
Issue number2
DOIs
StatePublished - Mar 1 2013

ASJC Scopus subject areas

  • Microbiology
  • Virology

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