Another decade of Trichuris muris research: An update and application of key discoveries.

Abstract

The mouse whipworm, Trichuris muris, has been used for over 60 years as a tractable model for human trichuriasis, caused by the related whipworm species, T. trichiura. The history of T. muris research, from the discovery of the parasite in 1761 to understanding the lifecycle and outcome of infection with different doses (high versus low dose infection), as well as the immune mechanisms associated with parasite expulsion and chronic infection have been detailed in an earlier review published in 2013. Here, we review recent advances in our understanding of whipworm biology, host-parasite interactions and basic immunology brought about using the T. muris mouse model, focussing on developments from the last decade. In addition to the traditional high/low dose infection models that have formed the mainstay of T. muris research to date, novel models involving trickle (repeated low dose) infection in laboratory mice or infection in wild or semi-wild mice have led to important insights into how immunity develops in situ in a multivariate environment, while the use of novel techniques such as the development of caecal organoids (enabling the study of larval development ex vivo) promise to deliver important insights into host-parasite interactions. In addition, the genome and transcriptome analyses of T. muris and T. trichiura have proven to be invaluable tools, particularly in the context of vaccine development and identification of secreted products including proteins, extracellular vesicles and micro-RNAs, shedding further light on how these parasites communicate with their host and modulate the immune response to promote their own survival.