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Review
. 2019 Jul 2:10:1499.
doi: 10.3389/fimmu.2019.01499. eCollection 2019.

M Cells: Intelligent Engineering of Mucosal Immune Surveillance

Affiliations
Review

M Cells: Intelligent Engineering of Mucosal Immune Surveillance

Andrea Dillon et al. Front Immunol. .

Abstract

M cells are specialized intestinal epithelial cells that provide the main machinery for sampling luminal microbes for mucosal immune surveillance. M cells are usually found in the epithelium overlying organized mucosal lymphoid tissues, but studies have identified multiple distinct lineages of M cells that are produced under different conditions, including intestinal inflammation. Among these lineages there is a common morphology that helps explain the efficiency of M cells in capturing luminal bacteria and viruses; in addition, M cells recruit novel cellular mechanisms to transport the particles across the mucosal barrier into the lamina propria, a process known as transcytosis. These specializations used by M cells point to a novel engineering of cellular machinery to selectively capture and transport microbial particles of interest. Because of the ability of M cells to effectively violate the mucosal barrier, the circumstances of M cell induction have important consequences. Normal immune surveillance insures that transcytosed bacteria are captured by underlying myeloid/dendritic cells; in contrast, inflammation can induce development of new M cells not accompanied by organized lymphoid tissues, resulting in bacterial transcytosis with the potential to amplify inflammatory disease. In this review, we will discuss our own perspectives on the life history of M cells and also raise a few questions regarding unique aspects of their biology among epithelia.

Keywords: Inflammatory Bowel Disease; endocytosis; epithelium; innate immunity; mucosal immunity.

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Figures

Figure 1
Figure 1
Confocal microscopy “en face” image of Peyer's patch, stained for M cells using UEA-1 lectin (green), with cytoplasmic expression of PGRP-S-dsRed reporter transgene evident below the surface of the follicle epithelium. Radial spoke distribution of M cells indicates origins in lineage-committed crypt stem cells.
Figure 2
Figure 2
Scanning Electron Microscopy image of Peyer's patch showing the uniform apical brush border surface of follicle epithelium, interspersed with M cells lacking microvilli which appear as “divots” in the surface.
Figure 3
Figure 3
Speculative model of M cell development in “Constitutive” (Top) or “Inflammation-inducible” (Bottom) settings. In the top figure, the “Two Step” model of M cell development is illustrated, showing “I. Lineage commitment,” and “II. Maturation of function”.
Figure 4
Figure 4
Confocal microscopy image of Peyer's patch showing PGRP-S-dsRed+ M cells (red) intimately associated with CX3CR1-EGFP+ subepithelial dome dendritic cells (green). M cell-derived dsRed+ cytoplasmic vesicles are evident in the dendritic cells.
Figure 5
Figure 5
Peyer's patch showing FAE M cells (red) with underlying array of RANKL+ stromal cells (yellow). Note that RANKL staining is strongest under the main concentration of M cells rather than near adjacent crypt stem cells [reprinted from Parnell et al. (96) with permission].

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