The pathogenesis ofShigella flexneriinfection: lessons fromin vitroand in vivo studies

Abstract

Shigella flexneriis a Gram–negative facultatively intracellular pathogen responsible for bacillary dysentery in humans. More than one million deaths occur yearly due to infections withShigellaspp. and the victims are mostly children of the developing world. The pathogenesis ofShigellacentres on the ability of this organism to invade the colonic epithelium where it induces severe mucosal inflammation. Much information that we have gained concerning the pathogenesis ofShigellahas been derived from the study ofin vitromodels of infection. Using these techniques, a number of the molecular mechanisms by whichShigellainvades epithelial cells and macrophages have been identified. in vivo models of shigellosis have been hampered since humans are the only natural hosts ofShigella. However, experimental infection of macaques as well as the murine lung and rabbit ligated ileal loop models have been important in defining some of the immune and inflammatory components of the disease. In particular, the murine lung model has shed light on the development of systemic and local immune protection againstShigellainfection. It would be naive to believe that any one model of Shigella infection could adequately represent the complexity of the disease in humans, and more sophisticated in vivo models are now necessary. These models require 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 of shigellosis will be designed.