title: Chronic intestinal inflammation induces stress-response genes in commensal Escherichia coli.
abstract: OBJECTIVE
  Intestinal microbes induce homeostatic mucosal immune responses, but can also cause inappropriate immune activation in genetically susceptible hosts. Although immune responses to bacterial products have been studied extensively, little is known about how intestinal inflammation affects functions of commensal luminal microbes.
  
  
  METHODS
  Microarrays and real-time polymerase chain reaction were used to profile transcriptional changes in luminal bacteria from wild-type and IL-10(-/-) mice monoassociated with a nonpathogenic, murine isolate of Escherichia coli (NC101, which causes colitis in gnotobiotic IL-10(-/-) mice). Colonic inflammation and innate and adaptive immune responses were measured in wild-type and IL-10(-/-) mice monoassociated with mutant NC101 that lack selected, up-regulated genes, and in IL-10(-/-) mice that were colonized with a combination of mutant and parental NC101. We measured intracellular survival of bacteria within primary macrophages from mice and resulting production of tumor necrosis factor.
  
  
  RESULTS
  Bacteria from IL-10(-/-) mice with colitis had significant up-regulation of the stress-response regulon, including the small heat shock proteins IbpA and IbpB that protect E coli from oxidative stress, compared to healthy, wild-type controls. In IL-10(-/-) mice, expression of ibpAB reduced histologic signs of colon inflammation, secretion of interleukin-12/23p40 in colonic explant cultures, serologic reactivity to NC101 antigens, and secretion of interferon-gamma by stimulated mesenteric lymph node cells. Infection of primary macrophages by bacteria that express ibpAB was associated with decreased intracellular survival and reduced secretion of tumor necrosis factor.
  
  
  CONCLUSIONS
  Chronic intestinal inflammation causes functional alterations in gene expression in commensal gut bacterium (E coli NC101). Further studies of these expression patterns might identify therapeutic targets for patients with inflammatory bowel diseases.
authors: Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7032, USA.
authors: Laura G
authors: LG
authors: Patwa
authors: Ting-Jia
authors: TJ
authors: Fan
authors: Sandrine
authors: S
authors: Tchaptchet
authors: Yang
authors: Y
authors: Liu
authors: Yves A
authors: YA
authors: Lussier
authors: R Balfour
authors: RB
authors: Sartor
authors: Jonathan J
authors: JJ
authors: Hansen
mesh_terms: D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013312:Stress, Physiological / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; C097578:IbpA protein, E coli; C097579:IbpB protein, E coli; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10