Impact of Rapamycin on Secondary Infection of Laboratory Mice (Mus musculus) with the Intestinal Nematode Heligmosomoides bakeri

The National Institutes of Health is studying rapamycin for over-the-counter use, as it may aid in slowing biological ageing. However, due to the immunosuppressive effects of rapamycin, over-the-counter use may be premature. Parasitic infections occur less frequently in the United States than in other countries; however, it is a reality that citizens are infected with parasites. With the current idea of providing people with a readily available dietary supplement to slow biological aging that also is a known immunosuppressant, it is important to discover the possibilities of rapamycin causing adverse effects on combating a parasitic worm infection. I studied the effects rapamycin ingestion on host susceptibility with associated immune measures, host food consumption and host body mass using a laboratory mouse-intestinal nematode model. Mice (Mus musculus) were fed a diet supplemented with rapamycin or a control diet and then, after a secondary infection with the intestinal nematode Heligmosomoides bakeri, we measured infection intensity, eosinophil production, and morphology of one primary lymphoid organ (thymus) and one secondary lymphoid organ (spleen). Impressively, mice fed rapamycin retained nearly eight times more worms than mice fed the control diet. Spleen mass reflected this difference in infection intensity, where infected mice had spleens that were 223% larger, however, spleen mass was not affected by diet. Mice fed rapamycin had 22% smaller thymi than those fed the control diet and infected mice had 32% smaller thymi than uninfected mice. These changes in thymi mass are in contrast with number of live thymocytes, where I found a significant interaction between diet and infection because uninfected rapamycin fed mice retained more live thymocytes than other experimental groups. However, mice that were infected and consumed rapamycin had the least number of thymocytes, which may be correlated with smaller thymi for those on rapamycin and mice that were infected. For eosinophil count, the expected increase with H. bakeri infection depended on the interaction between infection, diet and time. As expected, body mass increased over time during the experiment. Mouse initial and final body mass was not affected by diet or infection. Food intake overtime was largely similar among experimental groups. Taken together, this experiment showed that ingestion of rapamycin greatly suppressed the ability of mice to clear a secondary exposure of an intestinal parasitic nematode. This result should be considered when developing rapamycin as an over-the-counter supplement.