Fungal chitin is not an independent mediator of allergic fungal asthma severity.

Abstract

Chitin, a polysaccharide found in the fungal cell wall and the exoskeletons of house dust mites and cockroaches, has garnered attention as a potential immunoreactive allergen. Mammals have evolved to express chitin-degrading chitinases (acidic mammalian chitinase/AMCase and chitotriosidase) that may modulate immune responses to chitin. We have previously reported that mice deficient in AMCase (Chia-/-) demonstrated better lung function during allergic fungal asthma. As expected, we show that mice overexpressing AMCase (SPAM mice) had worse airway hyperreactivity (AHR) during allergic fungal asthma. We further demonstrate that chitin-positive Aspergillus fumigatus conidia are detectable in the allergic lung during chronic exposure. Lung function in Chia-/- and SPAM mice directly correlated with the level of chitinase activity during chronic fungal exposure (Chia-/- mice, negligible chitinase activity, lower AHR; SPAM mice, heightened chitinase activity, higher AHR), suggesting that the breakdown of chitin promoted AHR. However, chronic exposure of normal mice to purified A. fumigatus chitin resulted in only moderate inflammatory changes in the lung which were not sufficient to induce AHR. Moreover, despite having dramatic differences in chitinase activity, chronic exposure of Chia-/- and SPAM mice to purified A. fumigatus chitin likewise did not modulate AHR. Collectively, these results indicate that chronic exposure to fungal chitin alone is incapable of driving AHR. Furthermore, our data suggests that the chitinase-mediated degradation of chitin associated with A. fumigatus conidia may facilitate unmasking and/or liberation of other fungal cell wall components that drive inflammatory responses which contribute to AHR.