Effect of mite allergenic components on innate immune response: Synergy of protease (Group 1 & 3) and non-protease (Group 2 & 7) allergens

The major mite allergenic components of protease allergens (group 1,3) and non-protease allergens (group 2,7) derived from Dermatophagoides peronyssinus (Dp) and D. farinae (Df) are reported to be capable of sensitizing 80-90% of mite-allergic patients. Although protease and non-protease allergens have been demonstrated to trigger innate and adaptive immune responses through epithelium activation, the simultaneous or sequential effects of both groups of allergens has not been reported. Since all allergens are present in the mite crude extracts, it is important to determine whether these allergens can synergistically trigger the immune responses to cause airway inflammation. A total of 60 house dust mite (HDM)-allergic asthmatic patients were recruited to analyze their serum-specific IgE response to both groups of allergens. Recombinant protease allergen (Der p1 and Der p3) and non-protease allergens (Der p2 and Der p7) were used to activate the human airway epithelium cell (Beas-2B). The cells were analyzed for mRNA expression of IL-6/IL-8 and the culture supernatants were analyzed for neutrophil chemotactic activity (NCA). The results showed 48/60 (80%) HDM-allergic patients were sensitized to all allergenic components of Der p1, Der p2, Der f1, and Der f2. Most of the allergic patients were sensitized to both groups of allergens simultaneously. The associations of Der p1 with Der p2 were 83.3% (50/60) and Der f1 with Der f2 were 80% (48/60). When Beas-2B cells were cultured with Der p2 in conjunction with Der p1 and Der p3, the results showed that there was increased expression of IL-6/IL-8 in comparison with culture with allergen alone. There was only a trivial effect on IL-6/IL-8 expression when Der p2 was co-cultured with Der p7. Similar findings were obtained in the NCA measurement. When Beas-2B was cultured with Der p2 in conjunction with Der p1 and Der p3, there was increased NCA in comparison with culture with allergen alone. There were also trivial effects when Der p2 was co-cultured with Der p7. The allergens (Der p2 and Der p3)-induced IL-6/IL-8 expression and NCA released from Beas-2B could be downregulated by dexamethasone and transcription factor inhibitor SP600125. The allergenic components derived from Dp and Df can sensitize allergic patients simultaneously and activate epithelium through protease allergens (group 1, 3) and non-protease allergen (group 2) synergistically.