Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
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ORIGINAL ARTICLE
Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse Rinal Sahputra 1,2 & Emma A Murphy 1 & Ruth Forman 1 & Iris Mair 1 & Muhammad Z. H. Fadlullah 3 & Ari Waisman 4 & Werner Muller 1 & Kathryn J. Else 1 Received: 24 April 2020 / Revised: 24 June 2020 / Accepted: 17 July 2020 / Published online: 10 August 2020 # The Author(s) 2020
Abstract The IgMi mouse has normal B cell development; its B cells express an IgM B cell receptor but cannot class switch or secrete antibody. Thus, the IgMi mouse offers a model system by which to dissect out antibody-dependent and antibody-independent B cell function. Here, we provide the first detailed characterisation of the IgMi mouse post-Trichuris muris (T. muris) infection, describing expulsion phenotype, cytokine production, gut pathology and changes in T regulatory cells, T follicular helper cells and germinal centre B cells, in addition to RNA sequencing (RNA seq) analyses of wild-type littermates (WT) and mutant B cells prior to and post infection. IgMi mice were susceptible to a high-dose infection, with reduced Th2 cytokines and elevated B cell-derived IL-10 in mesenteric lymph nodes (MLN) compared to controls. A low-dose infection regime revealed IgMi mice to have significantly more apoptotic cells in the gut compared to WT mice, but no change in intestinal inflammation. IL-10 levels were again elevated. Collectively, this study showcases the potential of the IgMi mouse as a tool for understanding B cell biology and suggests that the B cell plays both antibody-dependent and antibody-independent roles post high- and low-dose T. muris infection. Key messages & During a high-dose T. muris infection, B cells are important in maintaining the Th1/Th2 balance in the MLN through an antibody-independent mechanism. & High levels of IL-10 in the MLN early post-infection, and the presence of IL-10-producing B cells, correlates with susceptibility to T. muris infection. & B cells maintain gut homeostasis during chronic T. muris infection via an antibody-dependent mechanism. Keywords Trichuris muris . B cells . IgMi mouse . Interleukin-10 . Th1/Th2 . Intestinal pathology
Introduction Worm infections affect about one third of the population worldwide with most infected people suffering chronic
infections and carrying worms asymptomatically for the rest of their lives [1, 2]. Trichuris trichiura (T. trichiura) is one of the most prevalent human parasites infecting approximately 500 million people, with the highest intensity and prevalence
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00109-020-01954-3) contains supplementary material, which is available to authorized users. * Rinal Sahputra [email protected] * Kathryn J. Else [email protected] 1
Division of Infection, Immunity and Respiratory Medicine, Lydia Becker Institute for Immunology, The University of Manchester, Manchester, UK
2
Division of Cell Matrix Biology and Regenerative Me
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