Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

Abstract

Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We show that Ym1 and Ym2 induce neutrophil accumulation through expansion of interleukin 17 (IL-17)-producing γδ T cells. While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, suggesting IL-17 regulation is an inherent feature of murine CLPs. Using a model of lung migrating nematode infection, we also found that IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. These studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.