Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella flexneri

Abstract

Invasion of the intestinal barrier by Shigella flexneri involves complex interactions with epithelial and phagocytic cells. Major perturbation of the signals that maintain epithelial integrity permits mucosal invasion, leading to tissue destruction. Expression of this invasive phenotype depends on the secretion of Ipa proteins (invasins), which can trigger entry of the pathogen into epithelial cells by causing massive rearrangement of the host cell cytoskeleton and cause macrophage apoptotic death by direct interaction of IpaB with interleukin-1beta (IL-1beta)-converting enzyme. This results in the killing of defense cells and in the release of IL-1beta. In vivo, bacteria translocate through the epithelial barrier, essentially via M cells of the follicle-associated epithelium in the colonic and rectal mucosa. Apoptotic death of macrophages in subepithelial tissues allows bacterial survival and triggers inflammation, which destabilizes epithelial structures and facilitates further bacterial entry. Once they are intracellular, bacteria multiply within the cytoplasm and move from cell to cell by an actin-dependent process.