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      Salivary mucins in host defense and disease prevention

      review-article
      1 , 2 , 2 , *
      Journal of Oral Microbiology
      Co-Action Publishing
      saliva, mucin, oral health, MUC5B, MUC7

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          Abstract

          Mucus forms a protective coating on wet epithelial surfaces throughout the body that houses the microbiota and plays a key role in host defense. Mucins, the primary structural components of mucus that creates its viscoelastic properties, are critical components of the gel layer that protect against invading pathogens. Altered mucin production has been implicated in diseases such as ulcerative colitis, asthma, and cystic fibrosis, which highlights the importance of mucins in maintaining homeostasis. Different types of mucins exist throughout the body in various locations such as the gastrointestinal tract, lungs, and female genital tract, but this review will focus on mucins in the oral cavity. Salivary mucin structure, localization within the oral cavity, and defense mechanisms will be discussed. These concepts will then be applied to present what is known about the protective function of mucins in oral diseases such as HIV/AIDS, oral candidiasis, and dental caries.

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          Most cited references91

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          Mucins in the mucosal barrier to infection

          The mucosal tissues of the gastrointestinal, respiratory, reproductive, and urinary tracts, and the surface of the eye present an enormous surface area to the exterior environment. All of these tissues are covered with resident microbial flora, which vary considerably in composition and complexity. Mucosal tissues represent the site of infection or route of access for the majority of viruses, bacteria, yeast, protozoa, and multicellular parasites that cause human disease. Mucin glycoproteins are secreted in large quantities by mucosal epithelia, and cell surface mucins are a prominent feature of the apical glycocalyx of all mucosal epithelia. In this review, we highlight the central role played by mucins in accommodating the resident commensal flora and limiting infectious disease, interplay between underlying innate and adaptive immunity and mucins, and the strategies used by successful mucosal pathogens to subvert or avoid the mucin barrier, with a particular focus on bacteria. Supplementary information The online version of this article (doi:10.1038/mi.2008.5) contains supplementary material, which is available to authorized users.
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            Muc5b is required for airway defence.

            Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.
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              Mucin structure, aggregation, physiological functions and biomedical applications

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                Author and article information

                Journal
                J Oral Microbiol
                J Oral Microbiol
                JOM
                Journal of Oral Microbiology
                Co-Action Publishing
                2000-2297
                22 December 2015
                2015
                : 7
                : 10.3402/jom.v7.29759
                Affiliations
                [1 ]Biological Sciences in Dental Medicine, Harvard University, Cambridge, MA, USA
                [2 ]Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
                Author notes
                [* ]Correspondence to: Katharina Ribbeck, Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Rm. 56-341, Cambridge, MA 02139, USA, Email: ribbeck@ 123456mit.edu
                Article
                29759
                10.3402/jom.v7.29759
                4689954
                26701274
                828746ef-4442-4477-b22b-a5a909e5c7c9
                © 2015 Erica Shapiro Frenkel and Katharina Ribbeck

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 September 2015
                : 16 November 2015
                : 17 November 2015
                Categories
                Review Article

                Microbiology & Virology
                saliva,mucin,oral health,muc5b,muc7
                Microbiology & Virology
                saliva, mucin, oral health, muc5b, muc7

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