Dynamic interactions between Heligmosomoides polygyrus bakeri, the gut microbiome, and the host immune system

Abstract

Parasitic worms have a long evolutionary history with humans. However, in the era of modern medicine, certain countries have virtually eradicated this class of infections. These same regions now tend to have much higher rates of diseases that arise from dysfunction of the immune system (i.e. autoimmune and allergic diseases). Over several decades, epidemiological studies and animal models have shown that parasitic worm infections can improve the outcomes of autoimmune and allergic diseases. To build upon this work, we investigate the ability of the parasitic worm Heligmosomoides polygyrus bakeri (H. poly) to influence the immune system. Infection of laboratory mice with this helminth has been shown to relieve the symptoms of various diseases stemming from immune dysfunction. H. poly resides in the gastrointestinal tract and has additionally been shown to alter the composition of the gut microbiome. Consequently, the effects of this parasite on models of autoimmune and allergic disease could partially or wholly depend on H. poly's modification of the gut microbiome. We investigate this complex relationship by first establishing a new method of deriving H. poly larvae which allows for infection in mice of variable gut microbiome status. In application of this method, we found that H. poly infection differs between conventional mice and those lacking a gut microbiome. The gut microbiome was found to significantly affect both gut physiology and worm expulsion. Based on previous results, we extended our study beyond the gut to determine how H. poly infection influences immunity in the lung. In doing so, we found that H. poly infection alters lung gene expression similar to that seen in allergic asthma. These alterations in lung gene expression were further found to be dependent on the gut microbiome. Taken together, this work underscores the intricate three-way relationship between parasitic worm, host immune system, and gut microbiome that is established upon infection. Moreover, our findings indicate that the impact of H. poly on the gut microbiome plays a crucial role in the broad effects of infection on the host immune system.