title: Shigella flexneri infection is dependent on villin in the mouse intestine and in primary cultures of intestinal epithelial cells.
abstract: Villin is an actin-binding protein present in intestinal and kidney brush borders. Villin has been shown to present in vitro Ca(2+)-dependent bundling and severing F-actin properties. The study of villin knock-out mice allowed us to show that while bundling of F-actin microfilaments is unaffected, this protein is important for the reorganization of the actin cytoskeleton elicited by various signals during both physiological and pathological conditions. Here, we studied the role of villin during infection by Shigella flexneri, the causative agent of bacillary dysentery. This bacterium induces the reorganization of the host actin cytoskeleton to penetrate into epithelial cells and spread from cell to cell. In vivo, we show that unlike newborn vil+/+ mice, which are sensitive to Shigella invasion, resulting in a destructive inflammatory response of the intestinal mucosa following intragastric inoculation, newborn vil-/- mice appear fully resistant to infection. Using primary cultures of intestinal epithelial cells derived from vil+/+ or vil -/- mice, we demonstrate that villin plays an essential role in S. flexneri entry and cell-to-cell dissemination. Villin expression is thus critical for Shigella infection through its ability to remodel the actin cytoskeleton.
authors: Institut Curie UMR 144, 75248 Paris cedex 05, France.
authors: Rafika
authors: R
authors: Athman
authors: Maria-Isabel
authors: MI
authors: Fernandez
authors: Pierre
authors: P
authors: Gounon
authors: Philippe
authors: P
authors: Sansonetti
authors: Daniel
authors: D
authors: Louvard
authors: Dana
authors: D
authors: Philpott
authors: Sylvie
authors: S
authors: Robine
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000382:microbiology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D012763:Shigella flexneri / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; C026615:villin