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Chitin Is a Size-Dependent Regulator of Macrophage TNF and IL-10 Production¹

Carla A. Da Silva^*, Cécile Chalouni, Adam Williams, Dominik Hartl^*, Chun G. Lee^* and Jack A. Elias^2,*,

^* Section of Pulmonary and Critical Care Medicine and Department of Immunology, Yale University School of Medicine, New Haven, CT 06519; Genentech, Inc., South San Francisco, CA 94080; and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520

Chitin is a ubiquitous polysaccharide in fungi, insects, and parasites. We hypothesized that chitin is a size-dependent regulator of innate immunity. To test this hypothesis, we characterized the effects of chitins of different sizes on murine bronchoalveolar or peritoneal macrophages. In these studies, large chitin fragments were inert, while both intermediate-sized chitin (40–70 µm) and small chitin (SC; <40 µm, largely 2–10 µm) stimulated TNF elaboration. In contrast, only SC induced IL-10 elaboration. The effects of intermediate-sized chitin were mediated by pathways that involve TLR2, dectin-1, and NF-B. In contrast, the effects of SC were mediated by TLR2-dependent and -independent, dectin-1-dependent pathways that involved the mannose receptor and spleen tyrosine kinase. Chitin contains size-dependent pathogen-associated molecular patterns that stimulate TLR2, dectin-1, and the mannose receptor, differentially activate NF-B and spleen tyrosine kinase, and stimulate the production of pro- and anti-inflammatory cytokines.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant HL081639.

² Address correspondence and reprint requests to Dr. Jack Elias, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, 300 Cedar Street (S441 TAC), New Haven, CT 06519-1612. E-mail address: jack.elias{at}yale.edu

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor; MO, macrophage; rAMcase, recombinant acidic mammalian chitinase; BC, big chitin; IC, intermediate chitin; SC, small chitin; SSC, super SC; Wt, wild type; BAL, bronchoalveolar lavage; Syk, spleen tyrosine kinase; PI, propidium iodide; DIC, differential interference contrast; MR, mannose receptor; NBD, NEMO-binding domain.

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The JI 2009 182: 3331-3332. [Full Text]