Histology, M Cell


Article Author:
Ryan Sauls


Article Editor:
Bryce Taylor


Editors In Chief:
Silvio de Melo Jr.
Vittorio Giuliano
Truptesh Kothari


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
1/9/2019 11:52:12 AM

Introduction

M cells (or microfold cells, a name given due to their unique structure) are specialized intestinal epithelial cells that are primarily found overlying GALT lymphoid follicles such as the Peyer’s patches in the ileum). These cells do not possess normal intestinal microvilli, in contrast to normal intestinal enterocytes (epithelial cells), and are specialized to sample macromolecules (antigens and pathogens). M cells function to sample and transport antigens/pathogens from the luminal surface to the sub-epithelium (a process also known as transcytosis), where macrophages and other immune cells process the antigen/pathogens. This is achieved by a unique cellular structure involving many basolateral membrane invaginations that allow for the macrophages and other immune cells to initiate an immune response.

M cells play a vital role in immunity allowing immune responses to occur in response to intestinal pathogens/antigens. It is likely that many, if not all, intestinal antigens are initially processed by M cells. Some note that a decrease in M cells leads to failing immunity, such as in old age or chemotherapeutic states. It has been noted that many pathogens exploit this immune surveillance system, using the M cells as a method to gain access to the bloodstream/other parts of the body. Several intestinal pathogens also specifically target M cells to avoid immune processing.

The unique method of M-cell, trans-epithelial transport is also being explored as an intestinal drug and vaccine delivery option. There is still much research being done involving M cells, and it is likely that in 5 years or less this topic will be further expanded.

Structure

M cells differ structurally from normal intestinal mucosal cells. M cells have apical microfolds, hence their alternate name, "microfold cells." These apical microfolds are poorly organized villi that have unique adhesion molecules to grab and sample luminal macromolecules. They have a thin glycocalyx, as opposed to the normally thick glycocalyx of other mucosal epithelial cells, that allows for adhesion but also does not impend the transport of molecules.[1][2] They have a unique intraepithelial invagination, or "pocket," on the basolateral surface that can also be seen via electron microscopy. These invaginations allow for macrophages and other immune cells to process the engulfed macromolecules in a short time, decreasing the time from transport to processing.[1][3]

Function

M cells function as sentries against intestinal toxins and/or pathogens, transporting them (trans-epithelial) to awaiting immune cells. M cells specialize in transcytosis (i.e., trans-epithelial transport). M cells uptake macromolecules (antigens, pathogens) from their apical surface (intestinal luminal surface) and transport these molecules, via vesicles, to the basolateral surface. This transport appears to be non-selective; however, some specialized adhesion and transport markers have been noted such as in the case of Vibrio uptake. There also are several basolateral invaginations which house macrophages and other immune cells. These immune cells process the presented molecules and deliver them further on to intestinal lymphoid follicles to initiate an immune response.[4][5][6]

This function has been known to be exploited as a method to gain entry into the body past the intestinal epithelial barrier.

Tissue Preparation

These cells lack typical enterocyte glycoproteins, mainly alkaline phosphatase and sucrase-isomaltase. These are used as negative markers for the identification of M cells. Due to their shortened, irregular microvilli, M cells also stain poorly for actin, villi, and other microvilli-associated proteins. This lack of villous staining can be further used to identify M cells.[1]

Histochemistry and Cytochemistry

Specific glycosylation patterns and lectins appear to vary among M cells, although some lectins have been used to characterize M cells. The UEA-1 and WBA lectins have been used to stain specifically for M cells, though it is not clear how commonly these lectins are involved with M cells.[1] M cells arise from LGLgr5 stem cells, found in the intestinal crypts. RANKL expression, among various tumor necrosis factors and other cytokines, is needed to signal for the development of M cells from the stem cells mentioned above. Deletions or functional modifications of RANKL have been linked to M cell deficiency.[7][8][9]

Microscopy Light

On light microscopy, M cells can be seen to have an absence of thick microvilli on their apical (luminal) surface and "pockets" of immune cells within their basolateral borders. Otherwise, electron microscopy and/or immunochemistry are used to identify these cells.[1]

Microscopy Electron

M cells have apical microfolds on electron microscopy (hence their alternate name, "microfold cells"). These apical microfolds are poorly organized villi that have unique adhesion molecules to grab and sample luminal macromolecules. They have a unique intraepithelial invagination (or "pocket") on the basolateral surface can also been seen via electron microscopy. These invaginations allow for macrophages and other immune cells to process the engulfed macromolecules.[1]

Clinical Significance

M cells are important for maintaining mucosal immunity function, particularly in the intestines. The immunologic reaction to many common intestinal pathogens, such as various Vibrio species, depends on initial uptake by M cells.[1][10] It has been noted that in aged mice there is a decrease in M cells along the intestinal epithelial border, possibly playing a role in age-related immune dysfunction.[7][11] M cell damage has also been implicated as in intestinal inflammation where damaged M cells allow for unregulated uptake of inflammatory molecules/pathogens into the sub-epithelial space, potentiating the inflammatory process.[12] M-cell deficiency, leading to immunodeficiencies, are noted in cases of RANKL deletion/modification due to its role in M cell development.[8]

Numerous intestinal pathogens also exploit the function of M cells to gain entry into the sub-epithelium, notable ones being Shigella and Listeria. Salmonella has been noted to target and destroy M cells, to both gain further entry into sub-epithelial tissues and avoid immunologic processing.Yersinia intestinal infections appear to use M cells as their primary method of entry into lymphoid follicles. HIV appears to use M cells as a method to spread and infect T cells based in mucosal lymphoid tissues.[1][4][13]

M cells are being explored as vaccine and drug routes. Mucosal administration of many drugs and vaccines are often cheaper and safer than other methods. This route of administration also has the added benefit of engaging both the mucosal and systemic immune responses. Several studies have shown an ability to use M cells specifically to administer vaccines/drugs; however, the exact role efficiency of this method is still being explored.[14][15][16]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Histology, M Cell - Questions

Take a quiz of the questions on this article.

Take Quiz
What is the term for antigen capture cells associated with GALT?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is a unique structural component of an M cell?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What M cell process does many Yersinia species exploit to gain access to lymphoid follicles?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient presents to the emergency department with severe diarrhea, fever, and abdominal cramps. Dehydration is noted and IV fluids are started. Stool samples are taken and sent to the lab. Salmonella typhimurium is suspected. What cell type does this pathogen specifically target to bypass the intestinal epithelium?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A histological specimen undergoes immunostaining and is noted to contain probable M cells. The absence of which of the following strengthens the probability of M cells being present?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Histology, M Cell - References

References

Corr SC,Gahan CC,Hill C, M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. FEMS immunology and medical microbiology. 2008 Jan     [PubMed]
Kraehenbuhl JP,Corbett M, Immunology. Keeping the gut microflora at bay. Science (New York, N.Y.). 2004 Mar 12     [PubMed]
Gebert A,Rothkötter HJ,Pabst R, M cells in Peyer's patches of the intestine. International review of cytology. 1996     [PubMed]
Owen RL, Uptake and transport of intestinal macromolecules and microorganisms by M cells in Peyer's patches--a personal and historical perspective. Seminars in immunology. 1999 Jun     [PubMed]
Kucharzik T,Lügering N,Rautenberg K,Lügering A,Schmidt MA,Stoll R,Domschke W, Role of M cells in intestinal barrier function. Annals of the New York Academy of Sciences. 2000     [PubMed]
Mabbott NA,Kobayashi A,Sehgal A,Bradford BM,Pattison M,Donaldson DS, Aging and the mucosal immune system in the intestine. Biogerontology. 2015 Apr     [PubMed]
Sehgal A,Kobayashi A,Donaldson DS,Mabbott NA, c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium. Immunobiology. 2017 Feb     [PubMed]
Rouch JD,Scott A,Lei NY,Solorzano-Vargas RS,Wang J,Hanson EM,Kobayashi M,Lewis M,Stelzner MG,Dunn JC,Eckmann L,Martín MG, Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids. PloS one. 2016     [PubMed]
Rios D,Wood MB,Li J,Chassaing B,Gewirtz AT,Williams IR, Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria. Mucosal immunology. 2016 Jul     [PubMed]
Rosner AJ,Keren DF, Demonstration of M cells in the specialized follicle-associated epithelium overlying isolated lymphoid follicles in the gut. Journal of leukocyte biology. 1984 Apr     [PubMed]
Gullberg E,Söderholm JD, Peyer's patches and M cells as potential sites of the inflammatory onset in Crohn's disease. Annals of the New York Academy of Sciences. 2006 Aug     [PubMed]
Schmucker DL,Thoreux K,Owen RL, Aging impairs intestinal immunity. Mechanisms of ageing and development. 2001 Sep 15     [PubMed]
Wang M,Gao Z,Zhang Z,Pan L,Zhang Y, Roles of M cells in infection and mucosal vaccines. Human vaccines     [PubMed]
Takahashi K,Yano A,Watanabe S,Langella P,Bermúdez-Humarán LG,Inoue N, M cell-targeting strategy enhances systemic and mucosal immune responses induced by oral administration of nuclease-producing L. lactis. Applied microbiology and biotechnology. 2018 Oct 11     [PubMed]
Azizi A,Kumar A,Diaz-Mitoma F,Mestecky J, Enhancing oral vaccine potency by targeting intestinal M cells. PLoS pathogens. 2010 Nov 11     [PubMed]
Owen RL, M cells as portals of entry for HIV. Pathobiology : journal of immunopathology, molecular and cellular biology. 1998     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Gastroenterology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Gastroenterology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Gastroenterology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Gastroenterology. When it is time for the Gastroenterology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Gastroenterology.