The Role of Intestinal Macrophages in Gastrointestinal Homeostasis: Heterogeneity and Implications in Disease

Abstract

Intestinal macrophages are the most abundant immune cells in our gut but understanding of their function is impeded by their heterogeneity. In this review we dissect different subtypes of intestinal macrophages and highlight their roles in several gastrointestinal (GI) disorders.Intestinal macrophages play a key role in the gut immune system and the regulation of gastrointestinal physiology, including gut motility and secretion. Their ability to keep the gut from chronic inflammation despite constantly facing foreign antigens has been an important focus in gastrointestinal research. However, the heterogeneity of intestinal macrophages has impeded our understanding of their specific roles. It is now becoming clear that subsets of intestinal macrophages play diverse roles in various gastrointestinal diseases. This occurs through a complex interplay between cytokine production and enteric nervous system activation that differs for each pathologic condition. Key diseases and disorders in which intestinal macrophages play a role include postoperative ileus, inflammatory bowel disease, necrotizing enterocolitis, as well as gastrointestinal disorders associated with human immunodeficiency virus and Parkinson's disease. Here, we review the identification of intestinal macrophage subsets based on their origins and functions, how specific subsets regulate gut physiology, and the potential for these heterogeneous subpopulations to contribute to disease states. Furthermore, we outline the potential for these subpopulations to provide unique targets for the development of novel therapies for these disorders.

High-throughput probing macrophage–bacteria interactions at the single cell level with microdroplets

“…Better understanding of the subpopulations of macrophages and their changes in maintaining endostasis is in great need. 34–36 Our fluorescence assays in the droplets have revealed that the different levels of extracellular secretion of NO by individual macrophages might be associated with the cellular heterogeneous properties. In the literature, the reports on detecting extracellular secretion of NO are few.…”

The Role of Tissue-Resident Macrophages in the Development and Treatment of Inflammatory Bowel Disease

“…The gastrointestinal tract harbors copious amounts of tissue macrophages, orchestrating innate and adaptive immune systems, helping to maintain homeostasis via tolerance to commensal microbes, as well as resisting potentially harmful pathogens ( Yip et al, 2021 ). In the past, the origin of tissue macrophages was considered to be the blood monocytes, deriving from precursors in the bone marrow ( van Furth et al, 1972 ; Bain and Mowat, 2014 ).…”

Inflammation and Impaired Gut Physiology in Post-operative Ileus: Mechanisms and the Treatment Options

“…4). 10,11,[111][112][113][114][115][116][117] These MMs lie in close proximity to neurons within the myenteric plexus, circular and longitudinal smooth muscle layers, and interstitial cells of Cajal. 111 MMs exist in different subsets based on their morphological (stellate and bipolar) structure, however their precise role is still ambiguous.…”