title: The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4.
abstract: Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC). NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother's expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria ("pioneer" bacteria) which preferentially stimulate intestinal host defense and anti-inflammation. One such "pioneer" organism is Bacteroides fragilis with a polysaccharide (PSA) on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2) response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2) which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC.
authors.affiliation: Laboratory of Rapid Diagnostic Technology for Animal Diseases, College of Veterinary Medicine, China Agricultural University, Beijing, China.|Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Meng
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Meiqian
authors.initials: M
authors.lastname: Weng
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Weishu
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Laboratory of Rapid Diagnostic Technology for Animal Diseases, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kasper
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: W Allan
authors.initials: WA
authors.lastname: Walker
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D016209:Interleukin-8 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011134:Polysaccharides / Q000276:immunology / Q000494:pharmacology*; D034622:RNA Interference; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D016209:Interleukin-8; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10