The Role of Flagellin in Anti-Bacterial Inflammatory Responses
We study the inflammatory response to the flagellin from enteroaggregative E. coli (EAEC), an emerging diarrheal pathogen. Bacterial flagellins are recognized by Toll-like receptor 5 (TLR5), leading to NF-kB activation, chemokine release, T-cell activation, and other inflammatory phenotypes. Our work is currently focused on several key projects:
- Studies of molecular inflammatory signalling in response to bacterial flagellin acting through Toll-like receptor 5 (TLR5).
- Identifying the role of flagellin/TLR5 interaction in the abnormal inflammatory responses that characterize Crohn’s disease
- Studies of flagellin-reactive effector and regulatory populations of T cells in the human gut in inflammatory bowel disease
- Pathogenic mechanisms of infectious diarrhea due to enteroaggregative E. coli
General consultative infectious diseases, with a particular interest in infectious diarrhea and tropical medicine
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Ivison SM, Khan MA, Graham NR, Bernales CQ, Kaleem A, Tirling CO, Cherkasov A, Steiner TS. A phosphorylation site in the Toll-like receptor 5 TIR domain is required for inflammatory signalling in response to flagellin. Biochem Biophys Res Commun. 2007 Jan 26;352(4):936-41.
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Khan MA, Kang J, Steiner TS. Enteroaggregative Escherichia coli flagellin-induced interleukin-8 secretion requires Toll-like receptor 5-dependent p38 MAP kinase activation. Immunology. 2004 Aug;112(4):651-60.
Donnelly MA, Steiner TS. Two nonadjacent regions in enteroaggregative Escherichia coli flagellin are required for activation of toll-like receptor 5. J Biol Chem. 2002 Oct 25;277(43):40456-61.
Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV,
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Steiner TS, Nataro JP, Poteet-Smith CE, Smith JA, Guerrant RL. Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells. J Clin Invest. 2000 Jun;105(12):1769-77.