Culp David J, Robinson Bently, Cash Melanie N, Bhattacharyya Indraneel, Stewart Carol, Cuadra-Saenz Giancarlo
From the Departments of Oral Biology and
From the Departments of Oral Biology and.
J Biol Chem. 2015 Jan 30;290(5):2993-3008. doi: 10.1074/jbc.M114.597906. Epub 2014 Dec 15.
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.
唾液在口腔固有免疫中发挥作用，可防止牙齿脱矿（即龋齿），龋齿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。凝胶形成性黏蛋白是唾液的主要成分。由于Muc19是小鼠中主要的唾液凝胶形成性黏蛋白，我们研究了Muc19基因敲除小鼠在与变形链球菌相互作用时唾液固有免疫功能的变化。当用变形链球菌和致龋饮食进行攻击时，Muc19基因敲除小鼠的总平滑面和沟裂面损伤分别比野生型小鼠高2倍多和1.6倍，而损伤的严重程度分别高达6倍和10倍。此外，Muc19基因敲除小鼠的口腔微生物群显示出较高水平的本土链球菌。结果强调了单一唾液成分在唾液固有免疫功能中的重要性。对变形链球菌与Muc19相互作用的体外研究（即黏附、聚集和生物膜形成）表明，Muc19对变形链球菌的聚集作用较差。然而，将Muc19添加到Muc19基因敲除小鼠唾液中时，聚集作用增强，这表明Muc19通过与结合变形链球菌的唾液成分形成异型复合物来协助细菌清除，从而代表了唾液凝胶形成性黏蛋白的一种新的固有免疫功能。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，并在腺黏液细胞和唾液中证实了MUC19糖蛋白。讨论了小鼠和人类在唾液凝胶形成性黏蛋白表达和功能方面的异同。
