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Journal Article
Mucin dynamics and enteric pathogens
2011
Overview
Key Points
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.
Secreted mucins are large, heavily
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-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.
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.
Cell surface mucins are heavily
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-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.
Deficiencies in secreted or cell surface mucins in animal models lead to increased pathology during infection.
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.
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.
The mucus barrier provides a crucial defence against commensal microorganisms and enteric pathogens. In this Review, McGuckin and colleagues describe the structure of the mucus barrier and discuss how the composition of the mucus layer is regulated under normal conditions and in response to infection.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adhesins
/ Animals
/ Bacteria
/ Bacterial Infections - immunology
/ Bacterial Infections - microbiology
/ Biomedical and Life Sciences
/ Cells
/ Colon
/ Decoys
/ Gastric Mucosa - microbiology
/ Gastrointestinal Diseases - immunology
/ Gastrointestinal Diseases - microbiology
/ Gastrointestinal Tract - immunology
/ Gastrointestinal Tract - metabolism
/ Gastrointestinal Tract - microbiology
/ Humans
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - microbiology
/ Microbiology in the Medical Area
/ Mikrobiologi inom det medicinska området
/ Mucin
/ Mucins
/ Mucus
/ Stomach
/ Virology
