Exploring the Significance of Autophagy in Host Defense in an Enteric Parasitic Infection

Abstract

Autophagy is a conserved cellular process that is responsible for degrading and recycling cytoplasmic constituents and has also emerged as a significant factor in modulating immune responses during enteric infections. This study investigates the role of autophagy in host defense during enteric parasitic infection, Trichuris muris, by focusing on the host defense, expulsion of worms, infection pathogenesis, and gut microbiota composition. Using C57BL/6 mice that are resistant and AKR mice that are susceptible to T. muris infection, we confirmed that when infected with T. muris, C57BL/6 mice can clear the infection almost completely by day 21 post-infection (p.i.). In contrast, AKR mice cannot, and therefore harbor a chronic infection within. Moreover, autophagy gene 7 floxed mice (Atg7fl/fl) and mice that are deficient in the autophagy protein, autophagy 7, in their intestinal epithelial cells (Atg7ΔIEC), were infected with T. muris and sacrificed on different time points. We observed that the Atg7fl/fl mice were able to almost clear the infection by day 21 p.i. but the Atg7ΔIEC mice were unable to clear infection by day 21 p.i. In vitro experiments consisted of exposing intestinal epithelial (HT-29) cell lines to T. muris excretory secretory products (ESPs) at different concentrations and also for different time-points, however, autophagy protein levels remained unchanged in those concentrations and time-points. Microbiota from uninfected and infected Atg7fl/fl and Atg7ΔIEC, analyzed by 16s rRNA sequencing revealed no significant differences in microbial composition among uninfected mice and minor differences in microbiota composition among T. muris infected mice.