title: Microbiota signalling through MyD88 is necessary for a systemic neutrophilic inflammatory response.
abstract: In the present study, we have found that intestinal flora strongly influence peritoneal neutrophilic inflammatory responses to diverse stimuli, including pathogen-derived particles like zymosan and sterile irritant particles like crystals. When germ-free and flora-deficient (antibiotic-treated) mice are challenged with zymosan intraperitoneally, neutrophils are markedly impaired in their ability to extravasate from blood into the peritoneum. In contrast, in these animals, neutrophils can extravasate in response to an intraperitoneal injection of the chemokine, macrophage inflammatory protein 2. Neutrophil recruitment upon inflammatory challenge requires stimulation by microbiota through a myeloid differentiation primary response gene (88) (MyD88) -dependent pathway. MyD88 signalling is crucial during the development of the immune system but depending upon the ligand it may be dispensable at the time of the actual inflammatory challenge. Furthermore, pre-treatment of flora-deficient mice with a purified MyD88-pathway agonist is sufficient to restore neutrophil migration. In summary, this study provides insight into the role of gut microbiota in influencing acute inflammation at sites outside the gastrointestinal tract.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Karmarkar
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D015054:Zymosan
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C433788:lipopolysaccharide, E. coli O26-B6; D015054:Zymosan
keywords: Intestinal flora; inflammation; neutrophils
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