Acidic chitinase primes the protective immune response to gastrointestinal nematodes

Nat Immunol. 2016 May;17(5):538-44. doi: 10.1038/ni.3417. Epub 2016 Apr 4.

Abstract

Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Chitinases / genetics
  • Chitinases / immunology*
  • Chitinases / metabolism
  • Chloride Channels / genetics
  • Chloride Channels / immunology
  • Chloride Channels / metabolism
  • Flow Cytometry
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / parasitology
  • Gene Expression / immunology
  • Hormones, Ectopic / genetics
  • Hormones, Ectopic / immunology
  • Hormones, Ectopic / metabolism
  • Host-Parasite Interactions / immunology
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism
  • Immunity / genetics
  • Immunity / immunology*
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism
  • Lectins / genetics
  • Lectins / immunology
  • Lectins / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Nematospiroides dubius / immunology
  • Nematospiroides dubius / physiology
  • Nippostrongylus / immunology
  • Nippostrongylus / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Strongylida Infections / immunology*
  • Strongylida Infections / metabolism
  • Strongylida Infections / parasitology
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / immunology
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Chloride Channels
  • Clca3a1 protein, mouse
  • Hormones, Ectopic
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13
  • Lectins
  • Retnlb protein, mouse
  • AMCase, mouse
  • Chitinases
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases