Dermatophagoides farinae upregulates the effector functions of eosinophils through αMβ2 integrin and PAR-2

RATIONALE: Even in subjects who are not sensitized to house-dust mite (HDM), allergic symptoms can be aggravated by exposure to dust, suggesting that innate immune responses may be involved in these processes. Since eosinophils express pathogen recognition receptors such as pattern recognition receptors (PRRs), HDM may directly upregulate eosinophil functions through these receptors. The objective of this study was to examine whether Dermatophagoides farina (Df), a representative HDM, or Der f 1, a major allergen of Df, modifies the effector functions of eosinophils.

METHODS: Eosinophils isolated from the blood of healthy donors or allergic patients were stimulated with Df or Der f 1, and their adhesion to recombinant human-intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of the eosinophil superoxide anion (O₂⁻) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation.

RESULTS: Df or Der f 1 directly induced eosinophil adhesion to ICAM-1, O₂⁻generation, and EDN release. Anti-αM or anti-β2 integrin antibodies or PAR-2 antagonists suppressed the eosinophil adhesion, O₂⁻ generation, and EDN release induced by Df or Der f 1. Eosinophils from allergic patients showed higher adhesion to ICAM-1 than those from healthy donors.

CONCLUSIONS: These findings suggested that Df and Der f 1 directly activate eosinophil functions through αMβ2 integrin and PAR-2. Eosinophil activation by HDM may play roles in the aggravation of allergic symptoms, not only in HDM-sensitized patients but also in non-sensitized patients.