Immunosuppressed patients are highly susceptible to invasive fungal infections (IFI) such as invasive pulmonary aspergillosis, which is predominantly caused by the fungus Aspergillus fumigatus. An important component of the fungal cell wall is chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc). Chitin is not produced by humans, however, the chitin degrading enzymes (chitinases) chitotriosidase (Chit-1) and acidic mammalian chitinase (AMCase) are. Chitinase is predominantly produced by activated macrophages, and may possibly aid in the defense against chitin-containing pathogens. We show that serum and bronchoalveolar lavage (BAL) chitinase levels are increased in patients with IFI, and in mice after pulmonary exposure to A. fumigatus conidia. Several different stimuli, including stimulation with chitin can lead to chitinase responses. In vitro stimulation of U937 human monocytes and RAW mouse macrophages with either chitin-particles (7-12 µm) or GlcNAc increased secreted and intracellular chitinase activity, the accumulation of intracellular Chit-1, and significantly increased the mRNA levels of Chit-1 and AMCase. Accordingly, we hypothesize that Chit-1 expression is regulated through a positive feedback mechanism involving the degradation of chitin to GlcNAc by host chitinases and GlcNAc recognition that in turn upregulates chitinase expression. This potential feedback mechanism of chitinase regulation may have utility in the diagnosis of IFIs.
- Copyright © 2011 by The American Association of Immunologists, Inc.