Acidic Mammalian Chitinase Negatively Affects Immune Responses during Acute and ChronicAspergillus fumigatusExposure
ABSTRACTChitin is a polysaccharide that provides structure and rigidity to the cell walls of fungi and insects. Mammals possess multiple chitinases, which function to degrade chitin, thereby supporting a role for chitinases in immune defense. However, chitin degradation has been implicated in the pathogenesis of asthma. Here, we determined the impact of acidic mammalian chitinase (AMCase) (Chia) deficiency on host defense during acute exposure to the fungal pathogenAspergillus fumigatusas well as its contribution toA. fumigatus-associated allergic asthma. We demonstrate that chitin in the fungal cell wall was detected at low levels inA. fumigatusconidia, which emerged at the highest level during hyphal transition. In response to acuteA. fumigatuschallenge,Chia−/−mice unexpectedly demonstrated lowerA. fumigatuslung burdens at 2 days postchallenge. The lower fungal burden correlated with decreased lung interleukin-33 (IL-33) levels yet increased IL-1β and prostaglandin E2(PGE2) production, a phenotype that we reported previously to promote the induction of IL-17A and IL-22. During chronicA. fumigatusexposure, AMCase deficiency resulted in lower dynamic and airway lung resistance than in wild-type mice. Improved lung physiology correlated with attenuated levels of the proallergic chemokines CCL17 and CCL22. Surprisingly, examination of inflammatory responses during chronic exposure revealed attenuated IL-17A and IL-22 responses, but not type 2 responses, in the absence of AMCase. Collectively, these data suggest that AMCase functions as a negative regulator of immune responses during acute fungal exposure and is a contributor to fungal asthma severity, putatively via the induction of proinflammatory responses.