Fungal Chitin is Not an Independent Mediator of Allergic Fungal Asthma Severity

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 () 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 conidia are detectable in the allergic lung during chronic exposure. Lung function in and SPAM mice is directly correlated with the level of chitinase activity during chronic fungal exposure ( 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 chitin resulted in only moderate inflammatory changes in the lung that were not sufficient to induce AHR. Moreover, despite having dramatic differences in chitinase activity, chronic exposure of and SPAM mice to purified 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 suggest that the chitinase-mediated degradation of chitin associated with conidia may facilitate unmasking and/or liberation of other fungal cell wall components that drive inflammatory responses that contribute to AHR. Humans with asthma sensitized to fungi often have more severe asthma than those who are not fungal-sensitized. Chitin makes up a significant portion of the cell wall of fungi and has been implicated as a pathogenic factor in allergic asthma. Ellis et al. demonstrate that chronic exposure to fungal chitin alone is unable to modulate lung function, even in the presence of differential lung chitinase activity.