Sensitizations to house dust mites (HDM) trigger strong exacerbated allergen-induced inflammation of the skin and airways mucosa from atopic subjects resulting in atopic dermatitis as well as allergic rhinitis and asthma. Initially, the Th2-biased HDM allergic response was considered to be mediated only by allergen B- and T-cell epitopes to promote allergen-specific IgE production as well as IL-4, IL-5, and IL-13 to recruit inflammatory cells. But this general molecular model of HDM allergenicity must be revisited as a growing literature suggests that stimulations of innate immune activation pathways by HDM allergens offer new answers to the following question: what makes an HDM allergen an allergen? Indeed, HDM is a carrier not only for allergenic proteins but also microbial adjuvant compounds, both of which are able to stimulate innate signaling pathways leading to allergy. This paper will describe the multiple ways used by HDM allergens together with microbial compounds to control the initiation of the allergic response through engagement of innate immunity. 1. Introduction House dust mites (HDM; Dermatophagoides sp.) are one of the commonest sources of airborne allergens worldwide and we can consider that HDM sensitization affects more than 15–20% of the population from industrialized countries [1]. Atopic patients exposed to HDM allergens develop potent inflammatory diseases in such allergic asthma, perennial rhinitis, and atopic dermatitis (AD) [2]. Experimental evidences suggest that HDM allergen-specific Th2 cells play the central role in the allergic inflammatory response inducing the production of allergen-specific IgE, the eosinophil recruitment in tissues, the permissiveness of endothelium for the recruitment of inflammatory cells to inflamed lungs, the production of mucus, and the modulation of the airway smooth muscle contraction. Notably, the Th2 cytokines IL-4, IL-5, IL-13 orchestrate these inflammatory processes: IL-4 is important for allergic sensitization and IgE production, eosinophil survival depends mainly on IL-5, whereas IL-13 has pleiotropic effects in the lungs, including a central role in the development of AHR and tissue remodeling [3]. Despite the high prevalence of HDM allergy, the precise nature of the cellular and molecular networks that initiate and regulate this Th2-biased response is still unclear. Recent advances clearly demonstrated that the HDM allergic response can no longer be considered as a unique dys-regulation of the adaptive immune system. Actually, a crosstalk between the innate and adaptive immune system
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