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TLR-2 and IL-17A in Chitin-Induced Macrophage Activation and Acute Inflammation¹

Carla A. Da Silva^*, Dominik Hartl^*, Wei Liu^*, Chun G. Lee^* and Jack A. Elias^2,*,

^* Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520-8057, and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8056

Chitin is a ubiquitous polysaccharide in fungi, insects, and parasites. To test the hypothesis that chitin is an important immune modulator, we characterized the ability of chitin fragments to regulate murine macrophage cytokine production in vitro and induce acute inflammation in vivo. In this study, we show that chitin is a size-dependent stimulator of macrophage IL-17A production and IL-17AR expression and demonstrate that these responses are TLR-2 and MyD88-dependent. We further demonstrate that IL-17A pathway activation is an essential event in the stimulation of some but not all chitin-stimulated cytokines and that chitin uses a TLR-2, MyD88-, and IL-17A-dependent mechanism(s) to induce acute inflammation. These studies demonstrate that chitin is a size-dependent pathogen-associated molecular pattern that activates TLR-2 and MyD88 in a novel IL-17A/IL-17AR-based innate immunity pathway.

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, P.O. Box 2080570, 300 Cedar Street (S441 TAC), New Haven, CT 06520-8057. E-mail address: jack.elias{at}yale.edu

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; WT, wild type; BAL, bronchoalveolar lavage.

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