Orchestrating house dust mite-associated allergy in the lung

Abstract

House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.

Figure 1

House dust mite allergenicity. The various components of HDM, and their associated fecal pellets and dust, which activate the immune system to initiate an inflammatory response, are illustrated.

Figure 2

Activation of airway epithelial cells. The figure shows the various pattern recognition receptors that are expressed on epithelial cells that can bind HDM-associated or induced ligands, including β-glucans, ATP, proteases (Der p 1, 3, 6 and 9) and endotoxin. Expression of these receptors on sub-epithelial fibroblasts and smooth muscle cells and the receptors for the epithelium-derived cytokines TSLP, IL-25 and IL-33 are depicted.

Figure 3

HDM-induced release of innate epithelial cytokines. Following exposure to HDM, the innate epithelial-derived cytokines TSLP, IL-33 IL-25 and CCL20 are released. Both innate and adaptive arms of the immune response are ultimately activated, resulting in immune-mediated pathology and airway hyper-reactivity.