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© The Rockefeller University Press, 0021-9525/1998//1003 $5.00
The Journal of Cell Biology, Volume 143, Number 4, , 1998 1003-1012

Interferon Inhibits a Src-mediated Pathway Necessary for Shigella-induced Cytoskeletal Rearrangements in Epithelial Cells

G. Duménil^*, J.C. Olivo^||, S. Pellegrini^*, M. Fellous^*, P.J. Sansonetti, and G. Tran Van Nhieu

^* Unité de Génétique Humaine, INSERM U276 and Unité de Pathogénie Microbienne Moléculaire, INSERM U389, Institut Pasteur, 75724 Paris Cedex 15, France; and ^|| European Molecular Biology Laboratory, Cell Biophysics Program, D-69117 Heidelberg, Germany

Shigella flexneri, the causative agent of bacillary dysentery, has the ability to enter nonphagocytic cells. The interferon (IFN) family of cytokines was found to inhibit Shigella invasion of cultured epithelial cells. We show here that IFN- inhibits a Src-dependent signaling cascade triggered by Shigella that leads to the reorganization of the host cell cytoskeleton. Immunofluorescence studies showed that IFN- inhibits Shigella-induced actin polymerization required for bacterial entry into cells. Phosphorylation of cortactin, a Src-substrate specifically tyrosyl-phosphorylated during Shigella entry, was inhibited by IFN-. Overexpression of a dominant interfering form of pp60c-src led to inhibition of Shigella-induced cytoskeletal rearrangements and decreased cortactin phosphorylation indicating a role for Src in Shigella entry. Also, Shigella uptake in cells that expressed constitutively active Src was unaffected by IFN- treatment. We conclude that Src kinase activity is necessary for Shigella invasion of epithelial cells and that IFN- inhibits this Src-dependent signaling pathway.

Key Words: Shigella • interferon • actin • cytoskeleton • Src

Abbreviations used in this paper: DAPI, 4,6-diamidino-2-phenylindole; FAK, focal adhesion kinase; IFN, interferon; mAb, monoclonal antibody; MAP kinase, mitogen activated kinase; TNF, tumor necrosis.

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