A mouse model for studies of adaptive immune response to Shigella flexneri 4806

Description Shigella species are the cause of bacillary dysentery and are responsible for significant global morbidity and mortality. There is no licensed vaccine against Shigella despite extensive efforts. One of the barriers to successful Shigella vaccine development is the lack of understanding of what immune cells mediate protection during infection. We hypothesize that Shigella activates T cells and/or induces antibody production which confer protection against secondary infection. However, wildtype mice are fully resistant to Shigella, and thus immunological studies of shigellosis have been hindered by the lack a physiologically relevant mouse model of infection. We recently discovered that mice lacking the NAIP–NLRC4 inflammasome are susceptible to oral Shigella infection and exhibit all the hallmarks of human shigellosis. We are taking advantage of this model to address the role of T cells during infection. We have shown that previous infection with Shigella protects against subsequent infections and that this infection is based on ability of Shigella to invade intestinal epithelial cells. Moreover, we observe cross protection between two different serotypes of Shigella suggesting that protection is against a conserved protein. Furthermore, we demonstrate that protection is dependent on CD4 T cells, but not CD8 T cells. We are currently evaluating the role of B cells in Shigella infection. We anticipate that our model may help inform the design of a successful Shigella vaccine.