Microfold cell

Last updated
Microfold cell
Details
System Immune system
Location Gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract
Function Antigen uptake
Identifiers
Latin epitheliocytus microplicatus
MeSH D000092303
TH H3.04.03.0.00010
FMA 62929
Anatomical terms of microanatomy

Microfold cells (or M cells) are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place. [1]

Contents

Unlike their neighbor cells, M cells have the unique ability to take up antigen from the lumen of the small intestine via endocytosis, phagocytosis, or transcytosis. Antigens are delivered to antigen-presenting cells, such as dendritic cells, and B lymphocytes. M cells express the protease cathepsin E, similar to other antigen-presenting cells. This process takes place in a unique pocket-like structure on their basolateral side. Antigens are recognized via expression of cell surface receptors such as glycoprotein-2 (GP2) that detect and specifically bind to bacteria. Cellular prion protein (PrP) is another example of a cell surface receptor on M cells. [2]

M cells lack microvilli but, like other epithelial cells, they are characterized by strong cell junctions. This provides a physical barrier that constitutes an important line of defense between the gut contents and the immune system of the host. Despite the epithelial barrier, some antigens are able to infiltrate the M cell barrier and infect the nearby epithelial cells or enter the gut. [3]

Structure

M cells are distinguished from other intestinal epithelial cells by their morphological differences. They are characterized by their short microvilli or lack of these protrusions on the cell surface. When they present microvilli, they are short, irregular, and present on the apical surface or pocket-like invagination on the basolateral surface of these cells. When they lack microvilli, they are characterized by their microfolds, and hence receive their commonly known name. These cells are far less abundant than enterocytes. These cells can also be identified by cytoskeletal and extracellular matrix components expressed at the edge of cells or on their cell surfaces, such as actin, villin, cytokeratin, and vimentin. [3]

Development

Factors promoting the differentiation of M cells have yet to be elucidated, but they are thought to develop in response to signals from immune cells found in developing Peyer's patches. [4] B cells have been implicated in the developmental of M cells, since they are also localized in high numbers in the follicular-associated epithelium (FAE). FAE lacking B cell populations results in a decrease in the number of M cell lining the Peyer's patches. Similarly, a human lymphoma cell line is also known to undergo transition from adenocarcinoma cells to M cells.

Though many studies have shown various cell types directing the differentiation of M cells, new research characterizes the molecular pathways that guide M cell differentiation. More recently, through loss-of-function and rescue-phenotype studies, RANKL is shown to be a receptor activator of NF-κB ligand and play a role in differentiation of M cells. RANKL is expressed throughout the small intestine, facilitates uptake of pathogens such as Salmonella, and is the most critical factor M cell differentiation. [5] Microbes found on intestinal epithelium are known to direct M cell development. For example, the type III secretion system effector protein SopB activates the transition of M cells from enterocytes. [6] M cells undergo the differentiation process for up to four days before reaching full maturation. Recent studies have suggested they arise distinctly from the lymphoid and myeloid lineages. [7]

Pathogens can take advantage of cell differentiation pathways in order to invade host cells. This is done by inducing differentiation of enterocytes into M cell type in gut epithelium. [1] In one case, the SopB effector protein mentioned above is secreted to trigger fast differentiation of enterocytes localized in the FAE by initiation of epithelial to mesenchymal transition in these cells. When SopB activates differentiation of enterocytes, it acts via the activation of the Wnt/b-catenin signaling pathway and triggers the RANKL and its receptor, implicated in regulating cell apoptosis. [8]

Function

M cells do not secrete mucus or digestive enzymes, and have a thinner glycocalyx, which allows them to have easy access to the intestinal lumen for endocytosis of antigens. The main function of M cells is the selective endocytosis of antigens, and transporting them to intraepithelial macrophages and lymphocytes, which then migrate to lymph nodes where an immune response can be initiated. [9]

Passive immunity

M cells play a role in passive immunity, or the transfer of active humoral immunity during and post pregnancy. Infants rely on antibodies specific to their mother's intestinal antigens, which move from the mother's gut and enter the breast milk. These antibodies are able to move into the milk supply through the lymphatic system. Even though the mechanism of this transport is not fully understood, it is hypothesized that dendritic cells and macrophages play the role of transport vehicles. In females that are not lactating, when M cells recognize antigen in the gut, they stimulate production of many Immunoglobulin A (IgA) antibodies. These antibodies are released into the gut mucosa, salivary glands, and lymph nodes. However, in females that are lactating, M cells recognize antigen and IgA is directed from the gut to the mammary gland. IgA traveling from the gut to breast milk supply is controlled by hormones, chemokines, and cytokines. Thus, the mammary gland and breast milk have critical roles alongside M cells in mucosal immune system. [10]

Clinical significance

M cells are exploited by several pathogenic gram-negative bacteria including Shigella flexneri , Salmonella typhimurium , and Yersinia pseudotuberculosis , as well as infectious prions, such as in bovine spongiform encephalitis (Mad-cow disease), as a way of penetrating the intestinal epithelium. Exploitation as a virulence factor depends upon the pathogen's ability to bind to M cells and thus guarantee penetration in that manner, as M cells sample intestinal contents. EPEC (see Pathogenic Escherichia coli) containing plasmids with genes for EAF ( Escherichia coli adherence factor) will adhere to M cells. They are also exploited by viruses such as Polio and Reovirus for dissemination. [11] CXCR4 tropic but not CCR5 tropic HIV has been noted to be able to bind to M cells and get transported across the epithelium by them. [12]

See also

Related Research Articles

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<span class="mw-page-title-main">Jejunum</span> Part of the small intestine

The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been previously digested by enzymes in the duodenum.

<span class="mw-page-title-main">Immunoglobulin A</span> Antibody that plays a crucial role in the immune function of mucous membranes

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<span class="mw-page-title-main">Plasma cell</span> White blood cell that secretes large volumes of antibodies

Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.

<span class="mw-page-title-main">Peyer's patch</span> Lymphatic tissue in the lower small intestine

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Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, nasopharynx, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells, dendritic cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue. MALT constitute about 50% of the lymphoid tissue in human body. Immune responses that occur at mucous membranes are studied by mucosal immunology.

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<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins, and peptides.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

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<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

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<span class="mw-page-title-main">Tuft cell</span>

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<span class="mw-page-title-main">Intestinal mucosal barrier</span>

The intestinal mucosal barrier, also referred to as intestinal barrier, refers to the property of the intestinal mucosa that ensures adequate containment of undesirable luminal contents within the intestine while preserving the ability to absorb nutrients. The separation it provides between the body and the gut prevents the uncontrolled translocation of luminal contents into the body proper. Its role in protecting the mucosal tissues and circulatory system from exposure to pro-inflammatory molecules, such as microorganisms, toxins, and antigens is vital for the maintenance of health and well-being. Intestinal mucosal barrier dysfunction has been implicated in numerous health conditions such as: food allergies, microbial infections, irritable bowel syndrome, inflammatory bowel disease, celiac disease, metabolic syndrome, non-alcoholic fatty liver disease, diabetes, and septic shock.

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<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

References

  1. 1 2 Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A (July 2013). "Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium". Mucosal Immunology. 6 (4): 666–677. doi:10.1038/mi.2013.30. PMC   3686595 . PMID   23695511.
  2. ↑ Miller H, Zhang J, Kuolee R, Patel GB, Chen W (March 2007). "Intestinal M cells: the fallible sentinels?". World Journal of Gastroenterology. 13 (10): 1477–1486. doi: 10.3748/wjg.v13.i10.1477 . PMC   1876659 . PMID   17461437.
  3. 1 2 Kanaya T, Ohno H (2014). "The Mechanisms of M-cell Differentiation". Bioscience of Microbiota, Food and Health. 33 (3): 91–97. doi:10.12938/bmfh.33.91. PMC   4098651 . PMID   25032083.
  4. ↑ Kraehenbuhl JP, Neutra MR (2000). "Epithelial M cells: differentiation and function". Annual Review of Cell and Developmental Biology. 16: 301–332. doi:10.1146/annurev.cellbio.16.1.301. PMID   11031239. Link
  5. ↑ Knoop KA, Kumar N, Butler BR, Sakthivel SK, Taylor RT, Nochi T, et al. (November 2009). "RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium". Journal of Immunology. 183 (9): 5738–5747. doi:10.4049/jimmunol.0901563. PMC   2922944 . PMID   19828638.
  6. ↑ Tahoun A, Mahajan S, Paxton E, Malterer G, Donaldson DS, Wang D, et al. (November 2012). "Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion". Cell Host & Microbe. 12 (5): 645–656. doi: 10.1016/j.chom.2012.10.009 . PMID   23159054.
  7. ↑ Ohno H, Kanaya T, Williams IR (November 2012). "M cell differentiation: distinct lineage or phenotypic transition? Salmonella provides answers". Cell Host & Microbe. 12 (5): 607–609. doi: 10.1016/j.chom.2012.11.003 . PMID   23159049.
  8. ↑ Tahoun A, Mahajan S, Paxton E, Malterer G, Donaldson DS, Wang D, et al. (November 2012). "Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion". Cell Host & Microbe. 12 (5): 645–656. doi: 10.1016/j.chom.2012.10.009 . PMID   23159054.
  9. ↑ Murphy KM (2012). Janeway's Immunobiology (8th ed.). New York: Garland Science. ISBN   978-0-8153-4243-4.
  10. ↑ Milligan L (April 2013). "From Mother's Gut to Milk". International Milk Genomics Consortium. Retrieved 2019-02-20.
  11. ↑ Ouzilou L, Caliot E, Pelletier I, Prévost MC, Pringault E, Colbère-Garapin F (September 2002). "Poliovirus transcytosis through M-like cells". The Journal of General Virology. 83 (Pt 9): 2177–2182. doi: 10.1099/0022-1317-83-9-2177 . PMID   12185271.
  12. ↑ Fotopoulos G, Harari A, Michetti P, Trono D, Pantaleo G, Kraehenbuhl JP (July 2002). "Transepithelial transport of HIV-1 by M cells is receptor-mediated". Proceedings of the National Academy of Sciences of the United States of America. 99 (14): 9410–9414. Bibcode:2002PNAS...99.9410F. doi: 10.1073/pnas.142586899 . PMC   123154 . PMID   12093918.
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