Chitin Recognition via Chitotriosidase Promotes Pathologic Type-2 Helper T Cell Responses to Cryptococcal Infection

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Humans often inhale potentially pathogenic fungi in the environment. While CD4+ helper T (Th) cells are required for protection against invasive disease, a subset of Th cells, called Th2 cells, are associated with increased mortality and allergy/asthma morbidity. Our study aimed to unravel the cellular and molecular basis of pulmonary Th2 cell induction in response to lethal infection with Cryptococcus neoformans. Antigen-presenting cells coordinate naïve Th cell priming and differentiation, but the precise leukocyte responsible for Th2 cell expansion to pulmonary cryptococcal infection has not been determined. Using an experimental mouse model of pulmonary cryptococcosis, we show that a subset of lung-resident dendritic cells is uniquely required for Th2 cell induction. We additionally sought to identify the molecular signal received by the host that allows dendritic cells to selectively induce Th2 cells. Since parasites and fungi elicit Th2 cell responses and both produce chitin, a molecule not found in vertebrates, we hypothesized that recognition of fungal chitin is a determinant of fungal disease. Here, we demonstrate that C. neoformans chitin and the host-derived chitinase, chitotriosidase, promote Th2 cell accumulation and disease. These findings highlight a promising target of next generation therapies aimed at limiting immunopathology caused by pulmonary fungal infection.

Vyšlo v časopise: Chitin Recognition via Chitotriosidase Promotes Pathologic Type-2 Helper T Cell Responses to Cryptococcal Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004701
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004701

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