Ricin and Shiga toxins: effects on host cell signal transduction

Abstract

Shiga toxins and ricin are potent inhibitors of protein synthesis. In addition to causing inhibition of protein synthesis, these toxins activate proinflammatory signaling cascades that may contribute to the severe diseases associated with toxin exposure. Treatment of cells with Shiga toxins and ricin have been shown to activate a number of signaling pathways including those associated with the ribotoxic stress response, Nuclear factor kappa B activation, inflammasome activation, the unfolded protein response, mTOR signaling, hemostasis, and retrograde trafficking. In this chapter, we review our current understanding of these signaling pathways as they pertain to intoxication by Shiga toxins and ricin.

Fig. 1

The MAPKinase signaling module

Fig. 2

The ribotoxic stress response by Shiga toxin and ricin results in MAPKinase activation which together with NFκB activation promotes expression of proinflammatory and pro-apoptotic genes

Fig. 3

Ricin induction of IL-1β results from the activation of MAPKinase and NFκB pathways which promote expression of Pro-IL-1β. Pro-IL-1β is converted to mature IL-1β via activation of the Nalp3 inflammasome

Fig. 4

The unfolded protein response