Shigella flexneri infection is dependent on villin in the mouse intestine and in primary cultures of intestinal epithelial cells

• Published in: Cellular microbiology Vol. 7; no. 8; pp. 1109 - 1116
• Main Authors: Athman, Rafika, Fernandez, Maria‐Isabel, Gounon, Pierre, Sansonetti, Philippe, Louvard, Daniel, Philpott, Dana, Robine, Sylvie
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2005; Hindawi Limited
• Subjects: Actins - metabolism; Animals; Animals, Newborn; Cells, Cultured; Cytoskeleton - metabolism; Dysentery, Bacillary - microbiology; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Cells - ultrastructure; Intestinal Mucosa - cytology; Intestines - metabolism; Intestines - microbiology; Intestines - ultrastructure; Mice; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Microscopy, Electron, Transmission; Shigella flexneri - metabolism; Shigella flexneri - physiology
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2005.00535.x

Summary Villin is an actin‐binding protein present in intestinal and kidney brush borders. Villin has been shown to present in vitro Ca2+‐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.