IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2

Fungus-induced asthmatic disease is characterized by persistent airway hype rreactivity and remodeling. Objective and design: To determine the role of IL-18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatu s-induced asthma. Methods: A. fumigatus-sensitized mice were depleted of IL-18 using a polycl onal anti-IL-18 antibody for 3 days after a conidia challenge. Results: Airway hyperresponsiveness and eosinophil numbers were significant ly elevated 3-30 days after conidia challenge compared to the normal serum- treated group. Histological evidence showed retention of A. fumigatus conid ia, airway remodeling, subepithelial fibrosis, and increased collagen depos ition in the lungs of IL-18-depleted mice at day 30 after the conidia chall enge. Prolonged retention of conidia in IL-18 depleted A. Jumigatus-sensiti zed mice was associated with decreased Toll-like receptor-2 (TLR-2) express ion compared with the control group. Conclusions: IL-18 modulates the innate immune response against A. fumigatu s conidia and prevents the development of severe fungus-induced asthmatic d isease.