The role of protease activity and monocyte subsets in initiating a Th2 response following allergen exposure

Abstract Allergy diseases are primarily caused by aberrant T helper 2 (Th2)-driven immune responses to allergens. During the primary sensitization phase, allergen specific Th2 cells are activated and become central players in orchestrating the subsequent development of allergic inflammation following secondary exposure to the same allergen. Still, the mechanisms by which the innate immune system detects allergens and initiates Th2 responses remain unclear. Protease activity is a feature common to many allergens, including house dust mite (HDM) and papain, a protein-digesting enzyme found in latex and papaya. Using models of Th2 airway inflammation induced by the allergens HDM and papain, we show that protease activity on allergens is required for the stimulation and clonal expansion of antigen specific T cells and their polarization towards a Th2 cell profile. Mechanistically, we found that protease activity was, in particular, required for enhanced migration of allergen-carrying dendritic cells (DCs) from the lung to draining lymph nodes and the subsequent activation of T cells throughout both phases of allergic disease. Our results suggest this occurs through CCR7 and CD86 expression. Further, we observed a decrease in monocytes and monocyte derived DCs when no protease activity was present within the allergens. Our results determine the early events involved in innate immune recognition of allergens and highlight a potential role for monocytic cells in initiating Th2 responses to allergens containing protease activity. Supported by National Institutes of Health grant 2R01AI116584 to B. León.