Bain, Calum C, Oliphant, Christopher J, Thomson, Carolyn A et al. (2 more authors) (2018) Pro-inflammatory role of monocyte-derived CX3CR1int macrophages in Helicobacter hepaticus-induced colitis. Infection and Immunity. e00579-17. ISSN 1098-5522
Abstract
Cells of the monocyte-macrophage lineage play important roles in the pathogenesis of inflammatory bowel diseases, but they are also present in the normal healthy intestine, where they are critical for maintaining homeostasis. It has been unclear whether the pro-inflammatory roles of intestinal macrophages reflect altered behaviour of the existing resident cells, or if they involve recruitment of a distinct cell type. Here we have explored these ideas using the model of colitis induced by Helicobacter hepaticus (Hh) in the context of neutralisation or deletion of interleukin 10 (IL-10). Granulocytes and monocytes made up most of the inflammatory myeloid infiltrates found in the colon of Hh-infected colitic mice, rising to a peak within 2 weeks of Hh inoculation, but taking several months to resolve completely. The inflammatory response was dependent on the combined presence of Hh and absence of IL-10, and was accompanied by increased production of inflammatory mediators such as IL-1β, TNFα, IL-6 and IL-23p19 by infiltrating myeloid cells, mostly relatively immature cells of the macrophage lineage that express intermediate levels of CX3CR1. In contrast, the population of mature CX3CR1hi macrophages did not expand as markedly during colitis, and these cells made little contribution to inflammatory mediator production. Taking into account their numerical dominance in the myeloid compartment, we conclude that newly recruited monocytes are the main source of pro-inflammatory mediators in colitis induced in the absence of IL-10 signalling, and that altered behaviour of mature macrophages is not a major component of this pathology.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Bain et al. |
Keywords: | Journal Article |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 09 Jan 2018 15:10 |
Last Modified: | 01 Dec 2024 01:11 |
Published Version: | https://doi.org/10.1128/IAI.00579-17 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1128/IAI.00579-17 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126064 |
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Filename: Infect._Immun._2017_Bain_IAI.00579_17.pdf
Description: Infect. Immun.-2017-Bain-IAI.00579-17
Filename: Infect._Immun._2018_Bain_.pdf
Description: Proinflammatory Role of Monocyte-Derived CX3CR1int Macrophages in Helicobacter hepaticus-Induced Colitis
Licence: CC-BY 2.5