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

• Published in: PloS one Vol. 12; no. 3; p. e0172738
• Main Authors: Jiang, Fei, Meng, Di, Weng, Meiqian, Zhu, Weishu, Wu, Wenxue, Kasper, Dennis, Walker, W Allan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2017; Public Library of Science (PLoS)
• Subjects: Activator protein 1; Animal diseases; Animal models; Animals; Bacteria; Bacteroides fragilis; Bacteroides fragilis - metabolism; Biology; Biology and Life Sciences; Breast milk; Cell cycle; Cells, Cultured; Cytokines; Dendritic cells; Disease Models, Animal; Enterocolitis; Enterocolitis, Necrotizing - prevention & control; Enterocytes; Enterocytes - cytology; Enterocytes - drug effects; Enterocytes - metabolism; Fetus - cytology; Fetuses; Gastrointestinal diseases; Health; Health care; Homeostasis; Hospitals; Humans; Hypotheses; Immunology; Infants; Inflammation; Inflammation - prevention & control; Interleukin 10; Interleukin 17; Interleukin 8; Interleukin-10 - metabolism; Interleukin-17 - metabolism; Interleukin-1beta - pharmacology; Interleukin-8 - analysis; Intestine; Laboratories; Lymphocytes; Lymphocytes T; Medical schools; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Milk; Morbidity; Necrosis; Necrotizing enterocolitis; Neonates; Organisms; Polysaccharides - immunology; Polysaccharides - pharmacology; Probiotics; Receptors; Research and Analysis Methods; RNA Interference; Rodents; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - antagonists & inhibitors; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transcription factors; Veterinary colleges; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0172738

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.