Complement Component 3C3 and C3a Receptor Are Required in Chitin-Dependent Allergic Sensitization to <named-content content-type="genus-species">Aspergillus fumigatus</named-content> but Dispensable in Chitin-Induced Innate Allergic Inflammation
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 Asper...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
American Society for Microbiology
2013
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/ef1080b5d70d4432b8f6ec4bc618dd2c |
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| Sumario: | 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 chitin-dependent allergic sensitization to Aspergillus requires C3aR signaling, which suppresses regulatory dendritic cells and T cells and induces allergy-promoting T cells. IMPORTANCE Asthma is one of the fastest growing chronic illnesses worldwide. Chitin, a ubiquitous polymer in our environment and a key component in the cell wall of fungal spores and the exoskeletons of insects, parasites, and crustaceans, triggers innate allergic inflammation. However, there is little understanding of how chitin is initially recognized by mammals and how early recognition of chitin affects sensitization to environmental allergens and development of allergic asthma. The complement system is evolutionarily one of the oldest facets of the early or innate warning systems in mammals. We studied whether and how complement components influence the recognition of chitin and shape the downstream sensitization toward fungal allergens. We show here that complement recognition of chitin plays a critical role in shaping the behavior of dendritic cells, which in turn regulate the function of T cells that mediate allergic responses to fungi. |
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