Key Points
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The gastrointestinal tract presents a continuous secreted and cell surface barrier to potential enteric pathogens. Specialized gastrointestinal epithelial cells secrete large amounts of mucin glycoproteins and antimicrobial molecules that, together, form the mucus barrier to infection. Although the lumen of the gastrointestinal tract contains large numbers of commensal microorganisms, the inner layers of mucus are sterile.
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Secreted mucins are large, heavily O-glycosylated glycoproteins that are produced by goblet cells. During their biosynthesis, mucins homo-oligomerize into complex polymeric networks that, when secreted, give mucus its viscoelastic properties.
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Antimicrobial molecules are produced throughout the gastrointestinal tract but particularly by the specialized Paneth cells in the small intestine. These molecules target different classes of pathogens and help keep the inner mucus layer sterile.
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Cell surface mucins are heavily O-glycosylated transmembrane glycoproteins that are present on the apical surface of all gastrointestinal epithelial cells. These mucins limit binding of pathogens to epithelial cells by steric hindrance and by acting as releasable decoys for microbial adhesins.
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Deficiencies in secreted or cell surface mucins in animal models lead to increased pathology during infection.
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Pathogens have evolved multiple strategies to penetrate the mucosal barrier, including: disruption and penetration of the mucus, avoidance of the mucus barrier, and disruption of epithelial integrity and epithelial production of barrier components.
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The production of components of the mucus barrier is influenced by the normal microbiota and by both innate and adaptive immune responses to pathogens. There are changes in the rate of mucus production and the content of mucus in response to infection; these factors are components of the mechanism of clearance of enteric pathogens and parasites.
Abstract
The extracellular secreted mucus and the cell surface glycocalyx prevent infection by the vast numbers of microorganisms that live in the healthy gut. Mucin glycoproteins are the major component of these barriers. In this Review, we describe the components of the secreted and cell surface mucosal barriers and the evidence that they form an effective barricade against potential pathogens. However, successful enteric pathogens have evolved strategies to circumvent these barriers. We discuss the interactions between enteric pathogens and mucins, and the mechanisms that these pathogens use to disrupt and avoid mucosal barriers. In addition, we describe dynamic alterations in the mucin barrier that are driven by host innate and adaptive immune responses to infection.
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Acknowledgements
M.A.M. and T.H.F. are supported by an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship and an NHMRC Senior Practitioner Fellowship, respectively. This work is supported by NHMRC project grant 543704.
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Glossary
- Commensal microorganism
-
A microorganism living in a mutually advantageous relationship with a mammalian host (for example, in the lumen of the gastrointestinal tract).
- Mucus
-
A viscous, highly hydrated fluid layer that overlies the mucosal surface and is rich in secreted mucin glycoproteins and other molecules involved in host defence against infection.
- Mucin
-
A cell surface or secreted glycoprotein that is characterized by the presence of a large filamentous domain which is rich in complex O-linked oligosaccharides.
- Antimicrobial molecule
-
One of a group of molecules that are produced by Paneth cells and other epithelial cells and that have a wide variety of structures. Many are small, cationic and amphipathic peptides or lectins, and are microbicidal because they interact with and disrupt microbial cell membranes. Many of these molecules can also be produced by granulocytes.
- Secreted mucin
-
A secreted glycoprotein with a central domain containing a dense array of O-linked oligosaccharides, and amino- and carboxy-terminal cysteine-rich domains that oligomerize the mucins into a large macromolecular complex, giving mucus its viscous properties.
- Goblet cell
-
A specialized secretory cell that manufactures secreted mucin glycoproteins and other components of the mucus.
- Paneth cell
-
A specialized intestinal secretory cell that manufactures antimicrobial molecules for secretion into the mucus.
- Theca
-
An intracellular collection of mucin granules that are packaged for secretion; the theca is responsible for the classical goblet cell morphology that is seen following conventional cell fixation.
- Lewis blood group antigen
-
A carbohydrate antigen that is found on the cell surface of red blood cells and also on epithelial glycolipids and glycoproteins, including mucins. Polymorphisms in glycosyltransferases determine the presence or absence of Lewis carbohydrates and also the precise isoforms of carbohydrate that are expressed on blood cells and the mucosae.
- Lamina propria
-
The tissue that underlies the mucosal epithelium and contains immune cells, connective tissue, and blood and lymphatic vessels.
- Rheological
-
Pertaining to the study of the properties of flow of matter.
- Cell surface mucin
-
A transmembrane glycoprotein with a dense array of O-linked oligosaccharides in its extracellular domain and with complex cytoplasmic domains that are involved in intracellular signalling. The extracellular domain of these mucins can be shed from the cell surface.
- Glycocalyx
-
An extracellular zone on the apical surface of mucosal epithelial cells that is composed of carbohydrate-rich transmembrane and secreted molecules, including cell surface mucin glycoproteins.
- Peyer's patch
-
An organized collection of tertiary lymphoid tissue directly underlying the intestinal epithelium; mainly found in the small intestine.
- Transcytose
-
To pass something (such as a microorganism) through a cell.
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McGuckin, M., Lindén, S., Sutton, P. et al. Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9, 265–278 (2011). https://doi.org/10.1038/nrmicro2538
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DOI: https://doi.org/10.1038/nrmicro2538
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