Key Points
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Mucins are highly O-glycosylated molecules that have gel-like properties. The mucin family consists of transmembrane mucins and gel-forming mucins. The transmembrane mucins cover the apical surfaces of the enterocytes and form the glycocalyx. The gel-forming mucins are secreted from goblet cells as large multimers that form the mucus skeleton and cover all epithelial surfaces.
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Mucus in the small intestine forms a diffusion barrier where antimicrobial substances keep the epithelium free from microorganism. Mucus in the colon forms a dense inner mucus layer that bacteria are unable to penetrate, creating a bacteria-free zone at the epithelial surface.
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Some, but not all, bacteria stimulate the formation of a functional mucus system with removable mucus in the small intestine and a stratified impenetrable inner mucus layer in colon.
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Mucus in the intestine creates a niche for bacteria, with digestible glycans providing a stable energy source, but mucus also traps and removes bacteria. Bacteria in loose mucus are planktonic and less virulent.
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The small intestinal goblet cells can sample luminal material during mucus secretion and transfer the antigens to lamina propria dendritic cells, something that also happens in the colon if bacterial numbers are decreased. This communication with the immune system has tolerogenic effects.
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Intestinal pathogens have mechanisms that allow them to circumvent the mucus protection to reach the epithelium. These include good motility and secretion of enzymes that can degrade the otherwise protease-resistant mucins.
Abstract
A number of mechanisms ensure that the intestine is protected from pathogens and also against our own intestinal microbiota. The outermost of these is the secreted mucus, which entraps bacteria and prevents their translocation into the tissue. Mucus contains many immunomodulatory molecules and is largely produced by the goblet cells. These cells are highly responsive to the signals they receive from the immune system and are also able to deliver antigens from the lumen to dendritic cells in the lamina propria. In this Review, we will give a basic overview of mucus, mucins and goblet cells, and explain how each of these contributes to immune regulation in the intestine.
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Acknowledgements
The work of the authors was supported by the Swedish Research Council, the Swedish Cancer Foundation, the Knut and Alice Wallenberg Foundation, the IngaBritt and Arne Lundberg Foundation, Sahlgren's University Hospital (ALF), the National Institute of Allergy and Infectious Diseases (U01AI095473), the Hasselblad Foundation, and the Swedish Foundation for Strategic Research.
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Glossary
- SEA domain
-
(Sea urchin sperm protein, enterokinase, and agrin domain) A domain that is found on the outside of the membrane in several transmembrane mucins and autocatalytically cleaved during folding in the endoplasmic reticulum.
- Cystic fibrosis transmembrane conductance regulator
-
(CFTR). An ion channel that transports chloride and bicarbonate ions. Defects in this channel cause cystic fibrosis.
- Dextran sulfate sodium (DSS)-induced colitis
-
A model of colitis induced in rodents by the addition of DSS to drinking water; this causes the inner colon mucus layer to become penetrable to bacteria, disrupts the epithelial layer and leads to intestinal inflammation.
- SAM pointed domain-containing Ets transcription factor
-
(SPDEF). A transcription factor that is a master regulator of goblet cell lineage differentiation and maturation.
- Goblet cell theca
-
The cluster of large mucin-filled granulae that are typically observed in goblet cells.
- Segmented filamentous bacteria
-
Bacteria that infect the small intestine of the mouse, but not humans, attaching to the enterocyte membranes; they support T helper 17 cell responses in the mouse intestine.
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Johansson, M., Hansson, G. Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol 16, 639–649 (2016). https://doi.org/10.1038/nri.2016.88
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DOI: https://doi.org/10.1038/nri.2016.88
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