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

Nat Immunol. 2014 Dec;15(12):1116-25. doi: 10.1038/ni.3023. Epub 2014 Oct 19.

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 found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitinase-3-Like Protein 1
  • Chitinases / immunology*
  • Cytotoxicity, Immunologic / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Glycoproteins / immunology*
  • Immunity, Innate / immunology
  • Inflammation / immunology
  • Interleukin-17 / immunology
  • Lectins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nematoda
  • Nematode Infections / immunology*
  • Neutrophil Infiltration / immunology*
  • Neutrophils / immunology
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • Transfection
  • beta-N-Acetylhexosaminidases / immunology*

Substances

  • Chil1 protein, mouse
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Interleukin-17
  • Lectins
  • Chitinases
  • Ym2 protein, mouse
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases