Disease tolerance as a defense strategy

Abstract

The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen's presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of "disease tolerance" into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.

Figure 1

Two types of fitness costs associated with infections. Pathogens can directly damage the host tissues. The immune system of the host reduces the pathogen burden through the resistance mechanism. The immune response can also damage the host tissues. The host can reduce fitness costs through tolerance mechanisms that reduce both the direct tissue damage by pathogens, and immunopathology.

Figure 2

Different tissues and physiological processes vary in tolerance capacity. Tissues depicted in red have the lowest tolerance to damage, the blue has an intermediate and the green has the highest tolerance capacity.

Figure 3

Tolerance capacity is a function of intrinsic damage susceptibility, repair capacity, functional autonomy, and damage sequela of different tissues and organs. Although tissues generally tend to fall at the same ends of the four spectra, the four characteristics do not necessarily correlate with each other.

Figure 4

When host fitness is plotted against pathogen burden, the slope of the lines reflects host tolerance to a given infection. In this example, the A is more tolerant to a given level of pathogen burden than B. An equivalent increase in pathogen burden will have greater negative impact on A than on B. A and B are typically different genotypes studied in the same environment. Alternatively, A and B can be two different environments where an organism with the same phenotype has different tolerance to infection. Modified from reference .