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The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context

Mair, Iris; Fenn, Jonathan; Wolfenden, Andrew; Lowe, Ann E.; Bennett, Alex; Muir, Andrew; Thompson, Jacob; Dieumerci, Olive; Logunova, Larisa; Shultz, Susanne; Bradley, Janette E.; Else, Kathryn J.

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Authors

Iris Mair

Jonathan Fenn

Andrew Wolfenden

Ann E. Lowe

Alex Bennett

Andrew Muir

Jacob Thompson

Olive Dieumerci

Larisa Logunova

Susanne Shultz

Janette E. Bradley

Kathryn J. Else



Contributors

Edward Mitre
Editor

Abstract

Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to ‘real world’ immune function.

Citation

Mair, I., Fenn, J., Wolfenden, A., Lowe, A. E., Bennett, A., Muir, A., …Else, K. J. (2024). The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context. PLoS Pathogens, 20(4), Article e1012119. https://doi.org/10.1371/journal.ppat.1012119

Journal Article Type Article
Acceptance Date Mar 13, 2024
Online Publication Date Apr 16, 2024
Publication Date Apr 16, 2024
Deposit Date Jun 3, 2024
Publicly Available Date Jun 4, 2024
Journal PLoS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 20
Issue 4
Article Number e1012119
DOI https://doi.org/10.1371/journal.ppat.1012119
Keywords Cytokines; Immune response; Parasitic diseases; Eggs; Trichuris; Mouse models; T helper cells; Principal component analysis
Public URL https://nottingham-repository.worktribe.com/output/34318867
Publisher URL https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012119

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Licence
https://creativecommons.org/licenses/by/4.0/

Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.





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