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

P A Louwe,C C Bain,G Perona-Wright,L Badiola Gomez,H Webster,S J Jenkins,S J Forbes

doi:10.1038/s41467-021-21778-0

P A Louwe, C C Bain + Show 5 more

Open Access

https://doi.org/10.1038/s41467-021-21778-0

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Abstract

Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment.

Highlights

Inflammation generally leads to recruitment of monocyte-derived macrophages
It has been proposed that competition for signals and cell-to-cell interactions that drive survival and proliferation of macrophages and expression of tissue-specific transcription factors dictates the balance between incumbent resident macrophages and infiltrating monocytes[16,17]
We demonstrate that inflammatory peritoneal macrophages recruited following sterile inflammation persist long-term but in an aberrant state of activation largely due to an inability to compete with incumbent macrophages for niche signals and inflammation-driven alterations in the peritoneal environment

Summary

Introduction

Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet elicited cells acquire a mature resident identity These macrophages have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. While a small number of seemingly ontogeny-related transcriptional differences may distinguish embryonic and monocytederived resident macrophages present within the same niche[12,14], limited evidence suggests that even these may be gradually reprogrammed over time[13,15] Based on these observations, it has been proposed that competition for signals and cell-to-cell interactions that drive survival and proliferation of macrophages and expression of tissue-specific transcription factors dictates the balance between incumbent resident macrophages and infiltrating monocytes[16,17]

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