Frank, S. A. and Schmid-Hempel, P. 2019. Evolution of negative immune regulators. PLoS Pathogens (in press).

Hosts must recognize pathogen invasion and respond rapidly. The need for speed requires a low threshold for triggering a response, causing occasional false alarms. Host immune systems therefore require strong negative regulators to shut down unnecessary responses. The evolutionary consequences of rapid trigger dynamics balanced by negative regulators has received little attention. Here, we emphasize four aspects that influence the evolutionary genetics of immunity: diverse gene families of rapidly acting triggers opposed by slower acting negative regulators; pathogen attack against negative regulators; diversifying selection of negative regulators by pathogen pressure; and heritability of immune-related disease from imbalance between triggers and negative regulators.