Crossroads between immune responses and physiological regulation: Metabolic control of resistance versus tolerance against disease

If a threat cannot be avoided, the organism has two defense options: it can try to eliminate the threatening agent or boost physiological mechanisms to tolerate the challenge and its consequences. Both strategies can be (and usually are) used at the same time. Fighting an infection, for instance, requires mounting immune responses to control pathogen burden as well as physiologic adaptations to tolerate stress and damage. Thus, the two strategies are connected and interdependent. We are starting to understand how the regulation of host metabolic physiology during disease impacts both the ability to resist pathogens’ burden and tolerate parenchymal tissue functional damage. Here, we review a number of recent publications that have begun to shed light on the physiological and immunological mechanisms that coordinate host defense and metabolic processes. In particular, we will cover the areas of energetic control, substrates utilization, and the regulatory signals that promote infectious disease tolerance.