title: Intimate adherence by enteropathogenic Escherichia coli modulates TLR5 localization and proinflammatory host response in intestinal epithelial cells.
abstract: Enteropathogenic Escherichia coli (EPEC) causes diarrhoeal disease by altering enterocyte physiology and producing mucosal inflammation. Many details concerning the host response against EPEC remain unknown. We evaluated the role of EPEC virulence factors on the inflammatory response through an analysis of bacterial recognition, cell signalling, and cytokine production using an in vitro epithelial cell infection model. Interestingly, we found that EPEC infection recruits Toll-like receptor 5 (TLR5) to the cell surface. We confirmed that type 3 secretion system (T3SS) and flagellin (FliC) are necessary for efficient extracellular regulated kinases 1 and 2 (ERK1/2) activation and found that intimin could down-regulate this pathway. Besides flagellin, intimin was required to keep nuclear factor kappa B (NF-κB) activated during infection. EPEC infection activated tumour necrosis factor alpha (TNF-α) production and induced interleukin (IL)-1β and IL-8 release. Virulence factors such as intimin, T3SS, EspA and fliC were required for IL-1β secretion, whereas intimin and T3SS participated in IL-8 release. Flagellin was essential for late secretion of TNF-α and IL-8 and intimin stimulated cytokine secretion. Initial adherence limited TNF-α release, whereas late attachment sustained TNF-α secretion. We conclude that intimin modulates TLR5 activation and intimate adherence alters the proinflammatory response.
authors.affiliation: Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), México DF, México.
authors.forename: H
authors.initials: H
authors.lastname: Salazar-Gonzalez
authors.forename: F
authors.initials: F
authors.lastname: Navarro-Garcia
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D018829:Adhesins, Bacterial / Q000502:physiology; D001422:Bacterial Adhesion / Q000276:immunology*; D058947:Bacterial Secretion Systems / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D029968:Escherichia coli Proteins / Q000502:physiology; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D055786:Gene Knockout Techniques; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D021381:Protein Transport; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; C102051:EspA protein, E coli; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D005408:Flagellin; D000072000:NF-KappaB Inhibitor alpha; C073819:eaeA protein, E coli; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3