Disease tolerance: concept and mechanisms

Abstract

Two distinct defense strategies provide a host with survival to infectious diseases: resistance and tolerance. Resistance is dependent on the ability of the host to kill pathogens. Tolerance promotes host health while having a neutral to positive impact of pathogen fitness. Immune responses are almost inevitably defined in terms of pathogen resistance. Recent evidence has shown, however, that several effects attributed to activation of innate and adaptive immune mechanisms, cannot be readily explained with the paradigm of immunity as effectors of microbial destruction. This review focuses on integrating the concept of disease tolerance into recent studies of immune system function related to the regulation and resolution of tissue damage, T cell exhaustion, and tolerance to innocuous antigen.

Figure 1

Overview of host tolerance and resistance measurement. A dose dependent curve can be generated from the relationship between host health (eg. survival) and pathogen burden, where vigor represents uninfected hosts. Host resistance (closed circle) is defined as a decrease in pathogen burden as host health (eg. survival) increases (linear relationship). Increases in host resistance are represented by increasing circle size. In comparison, host tolerance (open circle) is defined as an increase in host health (eg. survival) independently of pathogen burden. Increases in host tolerance are represented by increasing circle size and slope color (red= low tolerance, blue= high tolerance). Adapted from [1,4].