title: Chitin is a size-dependent regulator of macrophage TNF and IL-10 production.
abstract: 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 microm) and small chitin (SC; <40 microm, largely 2-10 microm) 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-kappaB. 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-kappaB and spleen tyrosine kinase, and stimulate the production of pro- and anti-inflammatory cytokines.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Da Silva
authors.forename: Cécile
authors.initials: C
authors.lastname: Chalouni
authors.forename: Adam
authors.initials: A
authors.lastname: Williams
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.forename: Chun G
authors.initials: CG
authors.lastname: Lee
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002686:Chitin / Q000737:chemistry* / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008970:Molecular Weight; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002686:Chitin