title: Host inflammatory response inhibits Escherichia coli O157:H7 adhesion to gut epithelium through augmentation of mucin expression.
abstract: Escherichia coli O157:H7, a major Shiga toxin-producing pathogen, has a low infectious dose and causes serious illness in humans. The gastrointestinal tract of cattle is the primary reservoir of E. coli O157:H7, and thus, it is critical to eliminate or reduce E. coli O157:H7 gut colonization. Given that E. coli O157:H7 produces effectors that attenuate inflammatory signaling, we hypothesized that the host inflammatory response acts to perturb E. coli O157:H7 intestinal colonization. Tumor necrosis factor alpha (TNF-α) treatment of HT-29 cells resulted in increased expression of inflammatory cytokine interleukin 1β (IL-1β), IL-8, and TNF-α genes and increased IL-8 protein and resulted in decreased adhesion of E. coli O157:H7. Similarly, E. coli O157:H7 adhesion to cattle colonic explants was reduced by TNF-α treatment. Irrespective of the presence of E. coli O157:H7, TNF-α enhanced activation of p65, the key mediator of NF-κB inflammatory signaling, whereas E. coli O157:H7 infection suppressed this pathway by inhibiting p65 activation in HT-29 cells. To further explore the mechanisms linking the inflammatory response to attenuated E. coli O157:H7 adhesion, mucin 2 (MUC2) expression was analyzed, considering that the intestinal mucus layer is the first defense against enteric pathogens and MUC2 is the major secretory mucin in the intestine. MUC2 expression in HT-29 cells was increased by TNF-α treatment and by E. coli O157:H7 infection. However, reducing mucin expression by blocking mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinases 1/2 (ERK1/2) and/or phosphatidylinositol 3-kinase (PI3K)/Akt signaling increased E. coli O157:H7 adherence to HT-29 cells. These data suggest that the inflammatory cytokine response acts to protect host epithelial cells against E. coli O157:H7 colonization, at least in part, by promoting mucin production.
authors.affiliation: School of Food Science, Washington State University, Pullman, Washington, USA.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Xue
authors.forename: Hanying
authors.initials: H
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D019453:Escherichia coli O157 / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism*; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha