How to live with the enemy: understanding tolerance to parasites

Abstract

How do we defend ourselves against pathogenic microbes and other parasites infecting us? Research on defence against parasites has traditionally focused on resistance--the ability to prevent infection or limit parasite replication. The genetics, physiology, and evolutionary ecology of such traits are now relatively well understood. During the last few years it has been realized that another, conceptually different type of defence also plays an important role in animal host-parasite interactions. This type of defence is called tolerance, and can be defined as the ability to limit the health effects of parasites without preventing infection or controlling parasite replication. Our understanding of the causes and consequences of variation in tolerance is, however, still rudimentary. Three recent studies shed light on these questions. In a study of HIV in humans, Regoes et al. show that an MHC class I gene affects not only resistance (as previously known) but also tolerance. In a study of voles, Jackson et al. identify a transcription factor mediating age differences in tolerance to macroparasites. Finally, Hayward et al. demonstrate that tolerance to intestinal parasites in sheep is under positive directional selection, but that most of the variation is environmentally induced rather than heritable. These studies increase our knowledge of the genetic and physiological sources of variation in tolerance, and how this variation affects Darwinian fitness. In addition, they illustrate different approaches to untangle tolerance from other factors determining the health effects of infectious disease.

Figure 1. Schematic illustration of how to separate the different host and parasite sources of genetic variation for virulence.

Dots are individual hosts. Lines represent reaction norms for different host or parasite genotypes. a) Virulence is the reduction in health a host experiences when infected. It is a function of the infection intensity (the realized infection intensity in this case is indicated with a vertical line on the x-axis) and the slope of the relationship between health and infection intensity. b) Variation among host genotypes for resistance. c) Variation among host genotypes for tolerance. d) Variation among parasite genotypes for “exploitation.” e) Variation among parasite genotypes for “per parasite pathogenicity.”