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

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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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Correspondence to Richard M. Locksley.

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