Mouse Tissue‐Resident Peritoneal Macrophages in Homeostasis, Repair, Infection, and Tumor Metastasis

Abstract

Large peritoneal macrophages (LPMs) are long-lived, tissue-resident macrophages, formed during embryonic life, developmentally and functionally confined to the peritoneal cavity. LPMs provide the first line of defense against life-threatening pathologies of the peritoneal cavity, such as abdominal sepsis, peritoneal metastatic tumor growth, or peritoneal injuries caused by trauma, or abdominal surgery. Apart from their primary phagocytic function, reminiscent of primitive defense mechanisms sustained by coelomocytes in the coelomic cavity of invertebrates, LPMs fulfill an essential homeostatic function by achieving an efficient clearance of apoptotic, that is crucial for the maintenance of self-tolerance. Research performed over the last few years, in mice, has unveiled the mechanisms by which LPMs fulfill a crucial role in repairing peritoneal injuries and controlling microbial and parasitic infections, reflecting that the GATA6-driven LPM transcriptional program can be modulated by extracellular signals associated with pathological conditions. In contrast, recent experimental evidence supports that peritoneal tumors can subvert LPM metabolism and function, leading to the acquisition of a tumor-promoting potential. The remarkable functional plasticity of LPMs can be nevertheless exploited to revert tumor-induced LPM protumor potential, providing the basis for the development of novel immunotherapeutic approaches against peritoneal tumor metastasis based on macrophage reprogramming.

Genetic variation in IL-4 activated tissue resident macrophages alters the epigenetic state to determine strain specific synergistic responses to LPS

“…We specifically focused on the large peritoneal cavity macrophages (LPM) that are F4/80 hi MHCII low and depend on the expression of Gata6 for their differentiation 40,41 . In response to inflammation, LPM will aggregate at specific sites in the peritoneal cavity to contain infection or mediate tissue repair 42 . IL-4 treatment of infection with nematode parasites can expand the LPM population through proliferation 43 , while activating the macrophages to adopt a tissue repair phenotype.…”

Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms

“…In the immune system, apoptotic B cells in the early germinal centers of lymphoid follicles locally activate follicular macrophages into classical tangible body macrophages for efferocytosis, which can prevent antibody-mediated autoimmune diseases ( 62 ). In mice, large peritoneal macrophages undergo efficient efferocytosis to maintain a homeostatic peritoneal microenvironment and promote self-tolerance ( 63 ). A “multi-omics” analysis of cardiac development/function from early embryo to adult mice revealed that a subpopulation of major histocompatibility complex class II-positive resident macrophages displayed arachidonic acid metabolism involved in efferocytosis, though the dysfunction of efferocytosis during this process was not clarified ( 64 ).…”

Porphyromonas gingivalis outer membrane vesicles shape trophoblast cell metabolism impairing functions associated to adverse pregnancy outcome

“…Pregnant mice were humanly killed on Day 14.5 of gestation. The ip dose (5 μg/kg) was calculated based on the in vitro studies here, on previous reports with locally administered peptides at Day 6.5 (Hauk et al, 2014(Hauk et al, , 2019 and the estimation of peritoneal fluid volume in female mice (Ardavín et al, 2023). Adjustment of the dose also involved testing a lower (10%) and a higher (10x) dose in a small group of pregnant animals at Day 6.5.…”