Journal
INFECTION AND IMMUNITY
Volume 86, Issue 2, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00579-17
Keywords
Helicobacter hepaticus; macrophages; monocytes; colitis
Categories
Funding
- Wellcome Trust [094763/Z/10/Z]
- Sir Henry Dale Fellowship - Wellcome Trust [206234/Z/17/Z]
- Sir Henry Dale Fellowship - Royal Society [206234/Z/17/Z]
- Wellcome Trust [206234/Z/17/Z, 094763/Z/10/Z] Funding Source: Wellcome Trust
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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 proinflammatory roles of intestinal macrophages reflect altered behavior of the existing resident cells, or whether they involve recruitment of a distinct cell type. Here, we have explored these ideas using the model of colitis induced by Helicobacter hepaticus in the context of neutralization or deletion of interleukin-10 (IL-10). Granulocytes and monocytes made up most of the inflammatory myeloid infiltrates found in the colon of H. hepaticus-infected colitic mice, rising to a peak within 2 weeks of H. hepaticus inoculation but taking several months to resolve completely. The inflammatory response was dependent on the combined presence of H. hepaticus and absence of IL-10 and was accompanied by increased production of inflammatory mediators such as IL-1 beta, tumor necrosis factor alpha (TNF-beta), 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 CX3CR1(hi) 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 proinflammatory mediators in colitis induced in the absence of IL-10 signaling and that altered behavior of mature macrophages is not a major component of this pathology.
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