Why do animals lose their appetites when sick? Should this inform our understanding of diet restriction therapies intended to increase lifespan? In this week's issue of the online open access journal PLoS Biology, scientists at Stanford University report another step taken towards understanding the link between immunity and aging.

Individuals can evolve two ways of surviving infections; they can resist the invading microbe by killing it, or they can tolerate the microbe and simply not become ill as microbe numbers rise. Most animals become anorexic (lose their appetites) when they are infected, but the effects this has on the host isn't well understood. Does the anorexia help the animal survive the infection or is it simply an unfortunate side effect? This story is complicated by the science of aging and diet restriction; moderate diet restriction appears to increase the lifespan of laboratory animals. Will medical treatments that mimic diet restriction and attempt to increase our lifespan interfere with this immune-regulated feeding response? "The answer seems to depend upon the infecting pathogen," argues senior author Dr David Schneider, of the Department of Microbiology & Immunology at Stanford University.

"We used infected fruit flies (Drosophila melanogaster) to answer these questions. We found that flies become anorexic when infected with some bacteria. To see how this anorexia might affect the fly's immune response we used two tricks. The first was to use a fly with a mutant taste receptor - this fly appears not to like the taste of fly food and doesn't eat much. We also limited the flies' diets by diluting their food. We found that diet restriction altered the fly's immune response and affected both resistance and tolerance. The fly became more tolerant of Salmonella infections, which suggests that anorexia could be a good thing that helps a host survive an infection. However, we found that diet restriction caused the flies to turn off an immune response that was critical for resisting Listeria infections and thus the flies died rapidly when infected with this microbe. "

These results provide one explanation for how anorexia might help an infected fly - the fly is better at tolerating the infection. These results suggest that diet restriction treatments will have complicated interactions with infections; they may help the infected animal survive some infections but can be deleterious in others. "Diet restriction might become a useful tool once we can determine the rules governing its interactions with different pathogens; however, diet restriction should be applied cautiously because it is clear, at least in flies, that diet restriction can lead to unwanted changes in immunity," Schneider concludes.

Funding: This work was funded by a National Science Foundation Graduate Research Fellowship, National Institutes of Health grant 1RO1AI069164, and an Ellison Medical Foundation Senior Scholar's Award in Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests statement: The authors declare that no competing interests exist.

Citation:
"The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila."
Ayres JS, Schneider DS (2009)
PLoS Biol 7(7): e1000150. doi:10.1371/journal.pbio.1000150

Source
PLoS Biology