The pathogenesis of Shigella flexneri infection: lessons from in vitro andin vivo studies

Shigella flexneri is a Gram-negative facultatively intracellular pathogen r esponsible for bacillary dysentery in humans, More than one million deaths occur yearly due to infections with Shigella spp. and the victims are mostl y children of the developing world. The pathogenesis of Shigella centres on the ability of this organism to invade the colonic epithelium where it ind uces severe mucosal inflammation. Much information that we have gained conc erning the pathogenesis of Shigella has been derived from the study of in v itro models of infection. Using these techniques, a number of the molecular mechanisms by which Shigella invades epithelial cells and macrophages have been identified. In vivo models of shigellosis have been hampered since hu mans are the only natural hosts of Shigella. However, experimental infectio n of macaques as well as the murine lung and rabbit ligated ileal loop mode ls have been important in defining some of the immune and inflammatory comp onents of the disease. In particular, the murine lung model has sited light on the development of systemic and local immune protection against Shigell a infection. It would be naive to believe that any one model of Shigella in fection could adequately represent the complexity of tho disease in humans, and more sophisticated in vivo models are now necessary. These models requ ire the use of human cells and tissue, but at present such models remain in the developmental stage. Ultimately, however; it is with such studies that novel treatments and vaccine candidates for the treatment and prevention o f shigellosis will bt designed.