ACUTE-INFLAMMATION CAUSES EPITHELIAL INVASION AND MUCOSAL DESTRUCTIONIN EXPERIMENTAL SHIGELLOSIS

The gram-negative pathogen Shigella flexneri causes bacillary dysenter y, an invasive disease of the human colonic mucosa. A major characteri stic of the infectious process is the occurrence of an acute inflammat ory reaction of mucosal tissues which is generally considered as a con sequence of primary invasion and destruction of colonic epithelial cel ls by the pathogen. Confirming in vitro demonstration that S. flexneri is unable to invade the apical pole of colonic cells and that polymor phonuclear (PMN) cells may assist them in reaching the basal side of e pithelial cells where they can invade, we have provided here in vivo e vidence that S. flexneri enters the epithelial barrier essentially thr ough the dome of lymphoid follicles at the early stage of infection an d that subsequent invasion and destruction of the epithelium is primar ily due to immigration of leukocytes, particularly PMN that destroy co hesion of the epithelial barrier. These conclusions are based on exper iments carried out in infected rabbit ligated intestinal loops, with s ome animals treated by an anti-CD18 monoclonal antibody that blocked i mmigration of leukocytes into infected tissues.