Asthma is a chronic inflammatory disease of the airways, driven by a Th2 immune response to allergens like house dust mite (HDM). While Th2 immune responses (IL-13 in particular) alone can induce allergic asthma, Th17 cytokines (IL-17) can exacerbate the disease. Although, the components of HDM that drive asthma remain unclear, HDM is a complex mixture including immunogenic structural moieties like carbohydrates. Such carbohydrate moieties can be recognized by pattern recognition receptors on dendritic cells (DCs) like C-type lectin receptors (CLRs). Recently, CLRs like Dectin-1 & Dectin-2 have been implicated in driving Th2 & Th17 responses against various infections. However, the role of carbohydrate recognition in modulation of HDM-induced allergic asthma remains unclear. Therefore we hypothesized that Dectin-1 & Dectin-2 induce Th2 & Th17 responses following HDM exposure. Surprisingly, Dectin-1 KO mice had exacerbated Th2 immune responses leading to enhance airway resistance. In contrast, mice in which Dectin-2 was blocked (using monoclonal antibody) had diminished HDM-induced Th2 immune responses and airway reactivity. Interestingly, neither Dectin-1 nor Dectin-2 modulated Th17 responses. Overall, our data suggests that while Dectin-1 protects against allergic asthma by negatively regulating Th2 immune responses, Dectin-2 promotes asthma by enhancing Th2 immune responses.
- Copyright © 2013 by The American Association of Immunologists, Inc.