Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent

P A Louwe1, L Badiola Gomez1, H Webster2

  • 1Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom.

Nature Communications
|March 20, 2021
PubMed

Insights

The environment, not genetics, dictates the fate of inflammation-elicited macrophages. Mild inflammation leads to immature macrophages, while severe inflammation promotes mature resident macrophage identity.

Area of Science:

  • Immunology
  • Cell Biology
  • Tissue Microenvironment Dynamics

Background:

  • Inflammation recruits monocyte-derived macrophages, but their differentiation and functional fate remain unclear.
  • The role of resident macrophages in regulating the identity of incoming inflammatory macrophages is not well understood.

Purpose of the Study:

  • To investigate the factors regulating the fate and identity acquisition of inflammation-elicited macrophages in the peritoneal cavity.
  • To determine the influence of inflammation severity and the resident macrophage population on elicited macrophage differentiation.

Main Methods:

  • Induction of mild and severe inflammation in the peritoneal cavity.
  • Long-term tracking and characterization of elicited macrophage populations.
  • Analysis of transcriptional and functional profiles of macrophages.
  • Assessment of the peritoneal cavity micro-environment.

Main Results:

  • Mild inflammation leads to persistent, immature elicited macrophages due to the presence of resident macrophages.
  • Severe inflammation causes resident macrophage ablation, followed by elicited cells acquiring a mature resident identity.
  • Inflammation-driven micro-environmental changes significantly impact macrophage phenotype and function.

Conclusions:

  • Macrophage fate is not predetermined but is dynamically regulated by the peritoneal cavity micro-environment.
  • The severity of inflammation and the status of resident macrophages critically influence elicited macrophage differentiation.
  • Environmental cues play a dominant role in shaping the identity and function of peritoneal macrophages.

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