Pro-inflammatory role of monocyte-derived CX3CR1int macrophages in Helicobacter hepaticus-induced colitis

Bain, C. C., Oliphant, C. J., Thomson, C. A., Kullberg, M. C. and Mowat, A. M. (2018) Pro-inflammatory role of monocyte-derived CX3CR1int macrophages in Helicobacter hepaticus-induced colitis. Infection and Immunity, 86(2), e00579-17. (doi: 10.1128/IAI.00579-17) (PMID:29203542) (PMCID:PMC5778360)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Bain, Mr Calum and Thomson, Miss Carolyn
Authors: Bain, C. C., Oliphant, C. J., Thomson, C. A., Kullberg, M. C., and Mowat, A. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN (Online):1098-5522
Published Online:04 December 2017
Copyright Holders:Copyright © 2017 Bain et al.
First Published:First published in Infection and Immunity 86(2):e00579-17
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
522461Resident and Inflammatory Macrophages in the IntestineAllan MowatWellcome Trust (WELLCOTR)094763/Z/10/ZIII -IMMUNOLOGY