HELMINTH INTERACTIONS WITH THE HOST IMMUNE SYSTEM: A COMPARATIVE STUDY OF MICE IN LABORATORY AND NATURAL SETTINGS

Abstract

The motivation for this study rests on the biome depletion theory, an extension of the hygiene hypothesis that posits that the increase in the prevalence of inflammatory diseases seen in developed countries is a result of the loss of coevolutionary partners from the human internal ecosystem. Specifically, the removal of intestinal helminths through improved sanitation measures and/or anthelmintic treatment has been suggested as a primary cause of the problem. This raises public health questions about which human populations might benefit from chronic helminth infection. However, experimentally investigating the potential benefits of helminths in human populations is fraught with ethical concerns because helminths have the potential to cause negative health outcomes as well (malnutrition, anemia, fatigue, etc.). Laboratory studies on animal models have frequently been used, but the laboratory setting is so inherently different from the natural environment that it is unclear to what extent these results will be generalizable. This study aims to provide a new protocol for studying immune mechanisms. Namely, this study runs parallel experiments on inbred mice in a laboratory and in a semi-natural environment, measuring various cytokine levels to characterize immune responses. This methodology enables an examination of the effects of heterogeneous environments on uninfected control mice and direct comparisons of the effects of helminth infection in the lab and in more natural environments. Our results indicate that the immunological effects observed in the lab are largely generalizable to the natural environment, but that effect size and/or absolute levels of cytokine expression vary by location. However, our results also suggest the presence of some immune effects associated with exposure to a natural environment. These effects are inherently missed by laboratory studies. Finally, the results indicate that the semi-natural environment methodology is a viable methodology for examining immunological mechanisms in a more natural setting.