Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response
Open Access
- 1 January 2001
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 107 (1), 99-109
- https://doi.org/10.1172/jci10501
Abstract
This study investigated whether soluble paracrine factors mediated Salmonella-induced IL-8 expression in polarized model intestinal epithelia. We found that the basolateral media of model epithelia that had been apically infected with Salmonella typhimurium for a short period (10 minutes) could activate IL-8 secretion in virgin model epithelia, demonstrating that a proinflammatory factor (PIF) was indeed present. Initial characterization found that PIF was a heat-stable protein with a molecular mass of about 50 kDa that acts on the basolateral, but not apical, surface of model intestinal epithelia to elicit IL-8 secretion. PIF was not present in the media of model epithelia stimulated with other inducers of IL-8 secretion (TNF-α or carbachol) but was present in S. typhimurium supernatants, indicating PIF is of bacterial origin. PIF was purified from bacterial culture supernatants by anion/cation exchange chromatography and SDS-PAGE and found by using microsequencing to be the protein flagellin. In support of this finding, flagellin-deficient S. typhimurium mutants did not secrete detectable levels of PIF (i.e., a bioactivity that induced IL-8 secretion when placed basolaterally on model epithelia). Furthermore, viable flagellin-deficient mutant organisms (fliC/fljB and flhD) failed to elicit IL-8 secretion when added apically to model intestinal epithelia. These findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial–S. typhimurium interaction, is likely a major means of activating a mucosal inflammatory response.Keywords
This publication has 52 references indexed in Scilit:
- Inactivation of the flagellin gene ofSalmonella entericaserotype Enteritidis strongly reduces invasion into differentiated Caco-2 cellsFEMS Microbiology Letters, 2000
- Salmonella typhimurium induces epithelial IL-8 expression via Ca2+-mediated activation of the NF-κB pathwayJCI Insight, 2000
- Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A4 analogs.JCI Insight, 1998
- Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease.Gut, 1996
- Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils.The Journal of cell biology, 1995
- PhoP/PhoQ transcriptional repression of Salmonella typhimurium invasion genes: evidence for a role in protein secretionMolecular Microbiology, 1995
- A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion.JCI Insight, 1995
- Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils.The Journal of cell biology, 1993
- Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccinesNature, 1981
- Construction of bacterial flagellaNature, 1975