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    Trichuris muris infection drives cell-intrinsic IL4R alpha independent colonic RELMα+ macrophages

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    Authors
    Forman, Ruth; orcid: 0000-0003-0374-6679; email: ruth.forman@manchester.ac.uk
    Logunova, Larisa; orcid: 0000-0002-7601-8296
    Smith, Hannah; orcid: 0000-0001-8911-9048
    Wemyss, Kelly; orcid: 0000-0003-0385-5920
    Mair, Iris
    Boon, Louis
    Allen, Judith E.; orcid: 0000-0002-3829-066X
    Muller, Werner; orcid: 0000-0002-1297-9725
    Pennock, Joanne L.; orcid: 0000-0002-8304-2905
    Else, Kathryn J.; orcid: 0000-0001-6660-055X; email: Kathryn.else@manchester.ac.uk
    Publication Date
    2021-07-30
    Submitted date
    2021-02-23
    
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    Abstract
    The intestinal nematode parasite Trichuris muris dwells in the caecum and proximal colon driving an acute resolving intestinal inflammation dominated by the presence of macrophages. Notably, these macrophages are characterised by their expression of RELMα during the resolution phase of the infection. The RELMα+ macrophage phenotype associates with the presence of alternatively activated macrophages and work in other model systems has demonstrated that the balance of classically and alternatively activated macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ alternatively activated macrophages are associated with the activation of macrophages via the IL4Rα. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known how colonic macrophages are activated towards an alternatively activated phenotype. Here, we address this important knowledge gap by using Trichuris muris infection, in combination with transgenic mice (IL4Rαfl/fl.CX3CR1Cre) and IL4Rα-deficient/wild-type mixed bone marrow chimaeras. We make the unexpected finding that education of colonic macrophages towards a RELMα+, alternatively activated macrophage phenotype during T. muris infection does not require IL4Rα expression on macrophages. Further, this independence is maintained even when the mice are treated with an anti-IFNγ antibody during infection to create a strongly polarised Th2 environment. In contrast to RELMα, PD-L2 expression on macrophages post infection was dependent on IL4Rα signalling in the macrophages. These novel data sets are important, revealing a surprising cell-intrinsic IL4R alpha independence of the colonic RELMα+ alternatively activated macrophage during Trichuris muris infection.
    Citation
    PLOS Pathogens, volume 17, issue 7, page e1009768
    Publisher
    Public Library of Science
    URI
    http://hdl.handle.net/10034/625552
    Type
    article
    Description
    From PLOS via Jisc Publications Router
    History: received 2021-02-23, accepted 2021-06-29, collection 2021-07, epub 2021-07-30
    Publication status: Published
    Funder: Medical Research Council; funder-id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N022661/1
    Funder: wellcome trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 106898/A/15/Z
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