To die or not to die: Cell decision-making in the face of viral threat

Paradoxically, the pro-inflammatory cytokine Tumor Necrosis Factor α (TNFα) simultaneously activates opposing pro-apoptotic and pro-survival signaling. We show that the activation of antagonistic pathways changes the properties of cell fate decision transitioning cells from a “slow and accurate” to “fast and error-prone” decision mode. Mathematical modeling predicts, and experiments in vitro and in vivo validate, that the regulation of the decision mode of non-immune cells by innate immune cell production of TNFα is key to prevent viral spread. Overall our results demonstrate how a collective phenotype emerges from the regulation of fundamental tradeoffs within cellular cognitive processes.