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

Jennifer Oyler-Yaniv, Alon Oyler-Yaniv, Evan Maltz and Roy Wollman ()
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Jennifer Oyler-Yaniv: University of California
Alon Oyler-Yaniv: University of California
Evan Maltz: University of California
Roy Wollman: University of California

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Rapid death of infected cells is an important antiviral strategy. However, fast decisions that are based on limited evidence can be erroneous and cause unnecessary cell death and subsequent tissue damage. How cells optimize their death decision making strategy to maximize 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 whole organ culture show that the regulation of the cell death 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.

Date: 2021
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DOI: 10.1038/s41467-021-23195-9

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