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Review
. 2023 Jan:253:41-53.
doi: 10.1016/j.imlet.2023.01.003. Epub 2023 Jan 7.

The intestinal microenvironment shapes macrophage and dendritic cell identity and function

Alessandra A Filardy  1 , Jesuino R M Ferreira  2 , Rafael M Rezende  3 , Brian L Kelsall  4 , Rafael P Oliveira  5
Affiliations
Review

The intestinal microenvironment shapes macrophage and dendritic cell identity and function

Alessandra A Filardy et al. Immunol Lett. 2023 Jan.

Abstract

The gut comprises the largest body interface with the environment and is continuously exposed to nutrients, food antigens, and commensal microbes, as well as to harmful pathogens. Subsets of both macrophages and dendritic cells (DCs) are present throughout the intestinal tract, where they primarily inhabit the gut-associate lymphoid tissue (GALT), such as Peyer's patches and isolated lymphoid follicles. In addition to their role in taking up and presenting antigens, macrophages and DCs possess extensive functional plasticity and these cells play complementary roles in maintaining immune homeostasis in the gut by preventing aberrant immune responses to harmless antigens and microbes and by promoting host defense against pathogens. The ability of macrophages and DCs to induce either inflammation or tolerance is partially lineage imprinted, but can also be dictated by their activation state, which in turn is determined by their specific microenvironment. These cells express several surface and intracellular receptors that detect danger signals, nutrients, and hormones, which can affect their activation state. DCs and macrophages play a fundamental role in regulating T cells and their effector functions. Thus, modulation of intestinal mucosa immunity by targeting antigen presenting cells can provide a promising approach for controlling pathological inflammation. In this review, we provide an overview on the characteristics, functions, and origins of intestinal macrophages and DCs, highlighting the intestinal microenvironmental factors that influence their functions during homeostasis. Unraveling the mechanisms by which macrophages and DCs regulate intestinal immunity will deepen our understanding on how the immune system integrates endogenous and exogenous signals in order to maintain the host's homeostasis.

Keywords: Colon; Diet-derived antigens; Environmental immunomodulators; Microbiota; Small intestine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.. Microenvironmental factors affecting intestinal macrophages and dendritic cells under homeostatic conditions.
Identifying surface molecules and local mediators that drive the differentiation and/or maintain the phenotype and function of intestinal macrophages (microbiota, IL-10, and amino acids from the diet; receptors: CX3CRI, CD163, F4/80, CD64, CD169) and dendritic cells (TLSP and PGE2; receptors: CD103, FLT3, XCRI). The gray triangle identifies molecules (flagellin, ATP, lactate, SCFA, RA and TGF-β) and receptors (CD11c, CD11b, SIRPα and MHC-II) common to the effector and tolerogenic functional modulation of intestinal macrophages and dendritic cells. TGF-β: transforming growth factor β; SIRPα: signal regulatory protein α; RA: retinoic acid, SCFA: short-chain fatty acids; ATP: adenosine triphosphate; Diet aa: Diet derived-amino acids; IL-10: interleukin 10; PGE2: prostaglandin E2; TSLP: thymic stromal lymphopoietin protein.
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