Protection from intestinal inflammation by bacterial exopolysaccharides Journal Article

Authors: Jones, S. E.; Paynich, M. L.; Kearns, D. B.; Knight, K. L.
Article Title: Protection from intestinal inflammation by bacterial exopolysaccharides
Abstract: Host inflammatory responses against pathogenic organisms can be abrogated by commensals; however, the molecular mechanisms by which pathogenesis is prevented are still poorly understood. Previous studies demonstrated that administration of a single dose of Bacillus subtilis prevented disease and inflammation by the enteric mouse pathogen Citrobacter rodentium, which causes disease similar to the human pathogen enteropathogenic Escherichia coli. No protection was observed when an exopolysaccharide (EPS)-deficient mutant of B. subtilis was used, suggesting that EPS are the protective factor. In this study, we isolated and characterized EPS and showed that they also prevent C. rodentium-associated intestinal disease after a single injection. Protection is TLR4 dependent because EPS-treated TLR4 knockout mice developed disease. Furthermore, protection could be conveyed to wild-type mice by adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice. We found that EPS specifically bind peritoneal macrophages, and because mice lacking MyD88 signaling in myeloid cells were not protected by EPS, we conclude that bacterial EPS prevent colitis in a TLR4-dependent manner that requires myeloid cells. These studies provide a simple means of preventing intestinal inflammation caused by enteric pathogens.
Journal Title: Journal of Immunology
Volume: 192
Issue: 10
ISSN: 1550-6606
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 4813
End Page: 4820
Language: eng
Notes: LR: 20150515; GR: F32 DK 92054/DK/NIDDK NIH HHS/United States; GR: R01 AI050260/AI/NIAID NIH HHS/United States; GR: R21 AI 098187/AI/NIAID NIH HHS/United States; GR: R21 AI098187/AI/NIAID NIH HHS/United States; GR: T32 AI007508/AI/NIAID NIH HHS/United States; JID: 2985117R; 0 (Myd88 protein, mouse); 0 (Myeloid Differentiation Factor 88); 0 (Polysaccharides, Bacterial); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); NIHMS576275; OID: NLM: NIHMS576275; OID: NLM: PMC4018721; 2014/04/16 [aheadofprint]; ppublish