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Review
. 2020 Aug;32(8):e13843.
doi: 10.1111/nmo.13843. Epub 2020 Mar 28.

Intestinal resident macrophages: Multitaskers of the gut

Maria Francesca Viola  1 , Guy Boeckxstaens  1
Affiliations
Review

Intestinal resident macrophages: Multitaskers of the gut

Maria Francesca Viola et al. Neurogastroenterol Motil. 2020 Aug.

Abstract

Background: Intestinal resident macrophages play a crucial role in homeostasis and have been implicated in numerous gastrointestinal diseases. While historically believed to be largely of hematopoietic origin, recent advances in fate-mapping technology have unveiled the existence of long-lived, self-maintaining populations located in specific niches throughout the gut wall. Furthermore, the advent of single-cell technology has enabled an unprecedented characterization of the functional specialization of tissue-resident macrophages throughout the gastrointestinal tract.

Purpose: The purpose of this review was to provide a panorama on intestinal resident macrophages, with particular focus to the recent advances in the field. Here, we discuss the functions and phenotype of intestinal resident macrophages and, where possible, the functional specialization of these cells in response to the niche they occupy. Furthermore, we will discuss their role in gastrointestinal diseases.

Keywords: enteric nervous system; gastrointestinal tract; lamina propria; muscularis externa; neuroimmune interaction; resident macrophages.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Anatomical distribution of intestinal resident macrophages. Intestinal resident macrophages are located within different layers of the gastrointestinal tract. Macrophages (green) are mostly found randomly displaced within the villi of the lamina propria and can, however, also be found associated to the epithelium and Paneth cells (pink). Deeper within the tissue, macrophages in the submucosa lie closely associated to submucosal neurons and blood vessels. Within the muscularis externa, stellate macrophages can be found in the myenteric plexus, and bipolar macrophages are interspaced between fibers of the circular and the longitudinal muscle. Finally, macrophages are also present in the serosa
Figure 2
Figure 2
Ontogeny of intestinal resident macrophages. Macrophages (green) in the gut consist in a balance of shortlived cells that derive from incoming Ly6Chigh monocytes (red) that differentiate into Cx3cr1+ MHCII+ macrophages (green), and long‐lived self‐maintaining macrophages (light blue) of embryonic origin
Figure 3
Figure 3
Functional heterogeneity of intestinal resident macrophages. Distinct subpopulations of macrophages carry out specialized functions in relation to the anatomical niche they occupy. A, Cx3cr1high macrophages (green) located below the intestinal epithelium sample the lumen and may participate in the development through the transfer of trapped antigens to CD103+ dendritic cells (orange) that then migrate to the mesenteric lymph nodes (MLNs) to instruct naive T cells. FoxP3+ regulatory T cells then migrate to the intestinal lamina propria to promote tolerance, where they are maintained by IL‐10 produced by resident macrophages. B, CD169+ macrophages are associated to the base of the intestinal crypt where they promote epithelial proliferation and Paneth cell (pink) differentiation. Depletion of macrophages leads to reduced epithelial proliferation and loss of LGR5+ intestinal stem cells. In DSS colitis, macrophages produce CCL8 to attract pro‐inflammatory monocytes from the blood stream. C, Depletion of long‐lived self‐maintaining macrophages leads to enteric neurodegeneration and disruption of blood vessel architecture in the submucosa. D, Macrophages within the myenteric plexus are maintained by CSF1 produced by enteric neurons. Conversely, enteric macrophages produce BMP2 which regulates intestinal peristalsis. Depletion of long‐lived self‐maintaining macrophages leads to loss of enteric neurons, impaired peristalsis and delayed transit
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