TNF controls a speed-accuracy tradeoff in the apoptotic decision to restrict viral spread

Early commitment to apoptosis is an important antiviral strategy. However, fast decisions that are based on limited evidence can be erroneous and cause unnecessary cell death and tissue damage. How cells optimize their decision making strategy to account for both speed and accuracy is unclear. Here we show that exposure to TNF, which is secreted by macrophages during viral infection, causes cells to change their decision strategy from "slow and accurate" to "fast and error-prone". Mathematical modeling combined with experiments in cell culture and mouse corneas show that the regulation of the apoptotic decision strategy is critical to prevent HSV-1 spread. These findings demonstrate that immune regulation of cellular cognitive processes dynamically changes a tissues tolerance for self-damage, which is required to protect against viral spread.