Centre for Bioscience, Manchester Metropolitan University, Manchester, United Kingdom; Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom.
Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.
Adv Parasitol. 2023;121:1-63. doi: 10.1016/bs.apar.2023.05.002. Epub 2023 Jul 6.
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.
鼠鞭虫，即 Trichuris muris，已被用于研究人类鞭虫病（由相关的鞭虫物种 Trichuris trichiura 引起）超过 60 年，是一种易于研究的模型。T. muris 的研究历史，从 1761 年寄生虫的发现，到对不同剂量（高剂量与低剂量感染）感染的生命周期和结果的理解，以及与寄生虫排出和慢性感染相关的免疫机制，在 2013 年发表的一篇早期综述中都有详细描述。在这里，我们综述了最近利用 T. muris 小鼠模型在鞭虫生物学、宿主-寄生虫相互作用和基础免疫学方面的理解进展，重点介绍了过去十年的发展。除了迄今为止构成 T. muris 研究主要内容的传统高/低剂量感染模型外，涉及实验室小鼠中滴注（重复低剂量）感染或野生或半野生小鼠感染的新型模型，使人们深入了解了免疫在多变量环境中如何原位发展，而新型技术的应用，如盲肠类器官的开发（使幼虫发育的离体研究成为可能），有望为宿主-寄生虫相互作用提供重要的见解。此外，T. muris 和 T. trichiura 的基因组和转录组分析已被证明是非常有价值的工具，特别是在疫苗开发和鉴定分泌产物（包括蛋白质、细胞外囊泡和 micro-RNAs）方面，进一步阐明了这些寄生虫如何与宿主进行交流并调节免疫反应以促进自身存活。
