The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila

Abstract

Infections initiate a signaling loop in which sick animals become anorexic, and the resulting change in diet alters the body's ability to fight infections in good and bad ways.

Abstract

Most infections induce anorexia but its function, if any, remains unclear. Because this response is common among animals, we hypothesized that infection-induced diet restriction might be an adaptive trait that modulates the host's ability to fight infection. Two defense strategies protect hosts against infections: resistance, which is the ability to control pathogen levels, and tolerance, which helps the host endure infection-induced pathology. Here we show that infected fruit flies become anorexic and that diet restriction alters defenses, increasing the fly's tolerance to Salmonella typhimurium infections while decreasing resistance to Listeria monocytogenes. This suggests that attempts to extend lifespan through diet restriction or the manipulation of pathways mimicking this process will have complicated effects on a host's ability to fight infections.

Author Summary

Two routes to decreasing susceptibility to infection are resistance (the ability to clear pathogens) and tolerance (the ability to limit damage in response to pathogens). Anorexia induced by sickness puts animals into a diet-restricted state, a state that is generally believed to extend lifespan. We asked whether anorexia induced by sickness would alter the immune response. We measured the effects of diet restriction on both resistance and tolerance to two different infections in the fruit fly, Drosophila melanogaster. In one case we found that infection induced anorexia and the resulting diet restriction increased tolerance to this infection, thereby increasing survival of flies infected with this pathogen; however, this is not a universal effect. In a second case we found another pathogen that induced anorexia but here diet restriction lead to a reduction in resistance that collapsed the immune response and caused the fly to die faster. The relationship between diet restriction and immunity is complicated and must be evaluated on a pathogen-by-pathogen basis.