# Retinoic acid modulates peritoneal macrophage function and distribution to enhance antibacterial defense during inflammation

## TL;DR

Retinoic acid boosts the ability of peritoneal macrophages to fight bacterial infections by enhancing their function and recruitment.

## Contribution

This study reveals how retinoic acid modulates macrophage function and distribution to improve antibacterial defense during inflammation.

## Key findings

- Retinoic acid increases macrophage phagocytic activity and delays functional decline.
- RA promotes the recruitment of small peritoneal macrophages and upregulates immune-related pathways.
- RA-loaded ZIF-8 nanoparticles prolong retinoic acid retention in macrophages, sustaining its effects.

## Abstract

Peritoneal macrophages, comprising large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), play a vital role in maintaining immune defenses during inflammation. However, the molecular mechanisms governing their responses, particularly the impact of retinoic acid (RA), remain poorly understood. This study aims to elucidate the role of RA in modulating macrophage function, distribution, and immune responses during bacterial infections.

A murine model of peritonitis was established using Escherichia coli expressing a tdTomato fluorescence marker. The effects of RA on macrophage phagocytic capacity, population dynamics, and transcriptomic profiles were assessed using immunofluorescence, flow cytometry, RNA sequencing, and quantitative PCR. Additionally, RA-loaded ZIF-8 nanoparticles were employed to investigate the sustained effects of RA delivery.

RA significantly enhanced macrophage phagocytic activity, delayed functional decline, and promoted the recruitment of SPMs in the peritoneal cavity. Transcriptomic analysis revealed upregulation of leukocyte migration and cell adhesion pathways in RA-treated SPMs. RA treatment also induced distinct gene expression profiles in macrophage subpopulations, reflecting its role in immune modulation. Notably, RA-loaded ZIF-8 nanoparticles prolonged RA retention within macrophages, sustaining its effects.

RA enhances antibacterial defense by modulating macrophage activity, providing new insights into immune regulation. These findings underscore the therapeutic potential of RA and its nanoparticle formulations in managing bacterial infections and inflammation.