Salivary Mucin 19 Glycoproteins INNATE IMMUNE FUNCTIONS IN STREPTOCOCCUS MUTANS-INDUCED CARIES IN MICE AND EVIDENCE FOR EXPRESSION IN HUMAN SALIVA
Salivary Mucin 19 Glycoproteins INNATE IMMUNE FUNCTIONS IN STREPTOCOCCUS MUTANS-INDUCED CARIES IN MICE AND EVIDENCE FOR EXPRESSION IN HUMAN SALIVA
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DOI：
10.1074/jbc.m114.597906
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发表时间：
2015-01-30
影响因子：
4.8
通讯作者：
Cuadra-Saenz, Giancarlo
中科院分区：
文献类型：
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作者：
Culp, David J.;Robinson, Bently;Cuadra-Saenz, Giancarlo
背景：我们在体内和体外对小鼠唾液Muc19进行了研究，以防止牙齿感染。结果：MUC19可减轻变形链球菌对牙科的感染，促进其聚集。提供了人类唾液MUC19的证据。结论：小鼠Muc19通过清除变形链球菌来限制其定植。意义：Muc19在清除方面的作用扩大了公认的唾液凝胶形成粘液的先天免疫功能。Saliva在口腔的先天免疫中发挥作用，防止牙齿脱矿(即龋齿)，这是一种与变形链球菌相关的高度流行的传染病，变形链球菌也是一种与心内膜炎和动脉粥样硬化斑块有关的病原体。形成凝胶的粘蛋白是唾液的主要成分。由于Muc19是小鼠唾液中主要的凝胶形成粘蛋白，我们研究了Muc19(-/-)小鼠在与变形链球菌相互作用时唾液天然免疫功能的变化。当受到变形链球菌和致龋性饮食的攻击时，Muc19(-/-)小鼠的光滑和沟槽表面病变总数分别是野生型的2倍和1.6倍，而病变的严重程度则分别高出6倍和10倍。此外，Muc19(-/-)小鼠的口腔微生物区系显示出更高水平的本土链球菌。结果强调了唾液中单一成分在唾液天然免疫功能中的重要性。对变形链球菌和Muc19相互作用(即黏附、聚集和生物膜形成)的体外研究表明，Muc19很难聚集变形链球菌。然而，在Muc19(-/-)小鼠的唾液中加入Muc19后，聚集性得到增强，这表明Muc19通过与唾液成分形成结合变形链球菌的异型复合体来帮助细菌清除，从而代表了唾液凝胶形成粘蛋白的一种新的先天免疫功能。在人类中，唾液MUC19的表达尚不清楚。我们在7名受试者的唾液腺中发现了MUC19转录本，并在腺体粘液细胞和唾液中发现了MUC19糖蛋白。讨论了小鼠和人类在唾液凝胶形成粘蛋白的表达和功能上的异同。
Background: We investigated murine salivary Muc19, in vivo and in vitro, to protect against dental infections. Results: Muc19 attenuates dental infections by Streptococcus mutans and promotes its aggregation. Evidence for human salivary MUC19 is presented. Conclusion: Murine Muc19 helps limit colonization via clearance of S. mutans. Significance: A role for Muc19 in clearance expands upon acknowledged innate immune functions of salivary gel-forming mucins.Saliva functions in innate immunity of the oral cavity, protecting against demineralization of teeth (i.e. dental caries), a highly prevalent infectious disease associated with Streptococcus mutans, a pathogen also linked to endocarditis and atheromatous plaques. Gel-forming mucins are a major constituent of saliva. Because Muc19 is the dominant salivary gel-forming mucin in mice, we studied Muc19(-/-) mice for changes in innate immune functions of saliva in interactions with S. mutans. When challenged with S. mutans and a cariogenic diet, total smooth and sulcal surface lesions are more than 2- and 1.6-fold higher in Muc19(-/-) mice compared with wild type, whereas the severity of lesions are up to 6- and 10-fold higher, respectively. Furthermore, the oral microbiota of Muc19(-/-) mice display higher levels of indigenous streptococci. Results emphasize the importance of a single salivary constituent in the innate immune functions of saliva. In vitro studies of S. mutans and Muc19 interactions (i.e. adherence, aggregation, and biofilm formation) demonstrate Muc19 poorly aggregates S. mutans. Nonetheless, aggregation is enhanced upon adding Muc19 to saliva from Muc19(-/-) mice, indicating Muc19 assists in bacterial clearance through formation of heterotypic complexes with salivary constituents that bind S. mutans, thus representing a novel innate immune function for salivary gel-forming mucins. In humans, expression of salivary MUC19 is unclear. We find MUC19 transcripts in salivary glands of seven subjects and demonstrate MUC19 glycoproteins in glandular mucous cells and saliva. Similarities and differences between mice and humans in the expression and functions of salivary gel-forming mucins are discussed.