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Chitin induces accumulation in tissue of innate immune cells associated with allergy

Nature volume 447, pages 92–96 (2007)Cite this article

Abstract

Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils1. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages2. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-β-d-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects3. Here, we show that chitin induces the accumulation in tissue of IL-4-expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase4, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B4, which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.

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Figure 1: Chitin induces accumulation of innate effector cells.
Figure 2: AMCase prevents chitin-induced eosinophil and basophil recruitment.
Figure 3: Chitin-induced eosinophil recruitment is independent of Stat6 and Rag, but is dependent on BLT1.
Figure 4: Chitin induces alternatively activated macrophages.

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Acknowledgements

We thank D. Stetson for assistance with recombinant protein production, G. Caughey, X. Xu and S. Akira for mice and reagents, N. Flores, C. McArthur and L. Stowring for expert technical assistance, and A. DeFranco and J. Bluestone for discussions. This work was supported by the NIH, the HHMI and the Sandler Asthma Basic Research Centre at UCSF.

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Author notes

  1. David Voehringer

    Present address: Present address: Institute for Immunology, University of Munich, Munich D-80336, Germany.,

Authors and Affiliations

  1. Departments of Medicine and Microbiology/Immunology, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0795, USA,

    Tiffany A. Reese, Hong-Erh Liang, David Voehringer & Richard M. Locksley

  2. Division of Rheumatology, Allergy and Immunology, Centre for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA,

    Andrew M. Tager & Andrew D. Luster

  3. Department of Molecular Cell Biology, Vrije Universiteit, 1091 BT, Amsterdam, The Netherlands,

    Nico Van Rooijen

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Correspondence to Richard M. Locksley.

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Reese, T., Liang, HE., Tager, A. et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447, 92–96 (2007). https://doi.org/10.1038/nature05746

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