The role of Dectin-1 in fungal asthma (64.5)

• Published in: The Journal of immunology (1950) Vol. 188; no. 1_Supplement; pp. 64 - 64.5
• Main Authors: Lilly, Lauren, Metz, Allison, Dunaway, Chad, Schwiebert, Lisa, Steele, Chad
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.64.5

Abstract Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. Although long considered a Th2 dominated disease, emerging data indicates that IL-17A and IL-22 may also contribute to asthma pathogenesis. Our laboratory has identified protective roles for Dectin-1 mediated beta-glucan recognition and Dectin-1 dependent IL-17A and IL-22 production during invasive A. fumigatus infection. Unexpectedly, in an allergic model of repeated lung exposure to live A. fumigatus conidia, we show that the absence of Dectin-1 resulted in markedly improved respiratory mechanics in the presence of reductions in multiple allergy-associated and inflammatory mediators. Intriguingly, attenuated lung IL-17A and IL-22 production in Dectin-1 deficient mice, but not Th2 cytokines, correlated with a better outcome. IL-22 deficiency reproduced the phenotype observed in Dectin-1 deficient mice after repetitive A. fumigatus exposure. We further identified IL-33 as a Dectin-1 and IL-22 dependent pro-allergic mediator. Collectively, our data suggests that during repetitive fungal exposure, beta-glucan recognition via Dectin-1 results in the generation of IL-17A and IL-22 responses as well as to the induction of IL-33 leading to the initiation of the allergic cascade. These results provide a novel link between infectious agents (fungi), new players (IL-22) and immunopathogenesis (IL-33) in severe asthma.