Toll Like Receptor-2 Modulates Both Innate and Adaptive Immune Responses During Chronic Fungal Asthma in Mice

Objective And Design: We investigated the effect of TLR2 gene deletion in a murine model of chronic fungal asthma.

Methods: TLR2 wildtype (TLR2(+/+)) and TLR2 deficient (TLR2(-/-)) mice were sensitized to soluble A. fumigatus antigens and challenged with live A. fumigatus conidia, and the extent of allergic airways disease was analyzed in both groups of mice at 3, 7, 14, and 30 days after conidia.

Results: At day 7 post-conidia, TLR2(-/-) mice exhibited significantly lower airway hyperresponsiveness, airway inflammation, and whole lung Th2 cytokine levels compared with the TLR2(+ / +) group. TLR2 deletion also significantly reduced mucus cell metaplasia and peribronchial fibrosis at day 30 after conidia. However, fungal material persisted in the TLR2(-/-) group, and at day 30 after conidia TLR2(-/-) mice exhibited enhanced airway neutrophil recruitment and airway hyperresponsiveness.

Conclusion: Thus, during chronic fungal asthma in mice, TLR2 is a major contributor to the maintenance of the adaptive Th2-cytokine driven and anti-fungal innate responses.