An Analysis of the Differential Effects of Dietary Protein on the Immunological Response to Infection by the Helminth Parasite Trichuris Muris

Abstract

ABSTRACTMalnutrition and intestinal helminth infections are chronic conditions that frequently coexist within the same geographic regions. While it is well known that malnutrition increases susceptibility to parasitic helminth infection, many of the immunological mechanisms underlying the relationship between host nutrition and helminth immunity remain largely unknown. Therefore, this study aimed to experimentally analyze the differential effects of dietary protein on the murine immune response to infection with the helminth parasite, Trichuris muris. Importantly, we conducted this experiment in a semi-natural environment in order to ascertain whether outdoor exposure influences the interaction between host protein intake and the immune response. C57BL/6 mice housed in a semi-natural facility were fed either a high protein or low protein diet and infected with a high dose of approximately 200 T.muris eggs. Over the course of 3 weeks post infection, blood and fecal samples were collected from each individual and analyzed for the production of Th2 type effectors IgG and mucin 5ac, respectively. At the end of the experiment, final caecum worm burdens were assessed and cytokine production was quantified from mesenteric lymph node cells via flow cytometry. Specifically, we measured the concentrations of Th2 associated cytokines IL-10 and IL-13 as well as the Th1 cytokine IFNγ, and the Th17 cytokine, IL-17. Results from these analyses demonstrate that protein deficiency significantly impairs the host Th2 immune response to infection, as evidenced by significant reductions in IL-13 and IgG in mice fed the low protein diet. Interestingly however, diet was not shown to significantly affect final worm burden, which could be a factor of environmentally induced alterations in parasite susceptibility and expulsion. Ultimately, this study provides important insight into the role of host nutrition in the immune response to helminth infection. This research also indicates the importance of studying these immunological interactions in a naturalistic setting that is more generalizable to conditions experienced by wild hosts outside the lab.