Abstract
Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80lowMHC-IIhigh phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations.
Highlights
Macrophages are resident cells found in almost all tissues of the body, where they assume specific phenotypes and develop distinct functions
GATA-6, an LPMrestricted transcription factor, regulates many peritoneal macrophage-specific genes (PMSGs), including those related to the maintenance of large peritoneal macrophages (LPMs) in peritoneal cavity (PerC) [40] and those that determine their function [40], metabolism, proliferation, and cell survival [39, 77]
LPMs appear to originate independently from hematopoietic precursors and retained the ability to proliferate in situ, maintaining physiological numbers [26, 36]
Summary
Macrophages are resident cells found in almost all tissues of the body, where they assume specific phenotypes and develop distinct functions. The phagocytic cells play similar roles in orchestrating the immune response and maintaining tissue homeostasis [11], they represent cell populations that are extremely heterogeneous [13], and the general classification of mononuclear cells in a unique system is currently under intense discussion [12, 14]. In this context, Guilliams et al suggested a classification of MPS cells based primarily on their ontogeny and secondary on their location, function, and phenotype, promoting a better classification under both steady state and inflammatory conditions [14]. This review will discuss recent advances in our understanding of peritoneal macrophage subsets characterization, origin and functions, and the accurate experimental approaches to analyze them
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