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