FIGURE 6.

Summary of proposed YopM and YopJ effects on IL-1β/IL-18 production and cell death in host cells. In the absence of YopJ and YopM, the cells respond to Y. pestis by expressing high levels of pro-IL-1β and pro-IL-18 and activating robust caspase-1 cleavage accompanied by pyroptotic cell death. YopM can inhibit IL-1β/IL-18 release and cell death by inhibiting inflammasome-mediated caspase-1 cleavage, but it has little effect on expression of pro-IL-1β/IL-18 or other cytokines not requiring inflammasome processing. In contrast, YopJ limits IL-1β/IL-18 production by suppressing expression of precursors and possibly by inducing rapid cell death, which may overshadow the cytoprotective effect of YopM. Additionally, YopJ alone triggers modest caspase-1 cleavage with some degree of IL-1β/IL-18 production, limited by the reduced levels of precursors, including pro-caspase-1 itself.