SALIARY IMMUNE RESPONSE TO COMMENSAL ORAL BACTERIA

对口腔共生细菌的唾液免疫反应

• 批准号: 2908092
• 负责人: MICHAEL F. COLE
• 金额: $ 25.13万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2908092
• 关键词: Streptococcus mitis; antibody; antigen antibody reaction; bacteria infection mechanism; bacterial antigens; breast feeding; clinical research; colostrums; dental plaque; enzyme linked immunosorbent assay; genetic strain; genotype; human subject; immune tolerance /unresponsiveness; immunoglobulin A; infant human (0-1 year); longitudinal human study; mouth; mucosal immunity; oral bacteria; phenotype; saliva; western blottings

The indigenous microbiota of the mouth and other mucosal surfaces exists in homeostasis with the host except when perturbed, the mucosal surface damaged or the immune system compromised. Then, commensal bacteria are capable of causing severe opportunistic infections. Adaptive humoral immunity at mucosal surfaces principally is effected by secretory immunoglobulin A (SIgA) that is thought to play a role in the regulation of commensal bacteria. However, despite the fact that saliva contains SIgA antibodies reactive with commensal bacteria, these microorganisms colonize and persist on mucosal and tooth surfaces. This suggests that indigenous oral bacteria are unaffected by, not subjected to, or are able to avoid immune elimination by mucosal antibodies. This assertion is supported by data published by others showing that the acquisition and composition of the oral and intestinal indigenous microbiota of mice lacking mucosal SIgA and their litter mates do not differ, and that colonization of mice by commensal enteric bacteria appears to generate a self-limiting mucosal immune response resulting in a state of chronic hypo-responsiveness. During the previous funding period we have demonstrated, in a longitudinal study of human infants from birth to two years of age, that the commensal oral bacterium, S. mitis biovar 1, induces a limited antibody response in saliva with salivary SIgA antibodies reactive with this bacterium showing a significant decline from birth to two years of age. Furthermore, this bacterium demonstrated extensive genetic diversity and evidence of clonal replacement. Concomitantly, Western blots of envelope antigens of type strains of this bacterium showed a similar high degree of variability. In this competing continuation, the hypothesis to be tested is that commensal bacteria persist in the mouth by inducing a limited salivary SIgA antibody response due to antigenic variation mediated via clonal replacement. Employing a longitudinal study of infants from birth to 12 months, the Specific Aims are to (1) analyze the clonal diversity of S. mitis biovar 1 obtained from shedding surfaces within the infants' mouth and (2) analyze the diversity of SIgA antibodies in each infants' saliva reactive with their own S. mitis biovar 1 isolates. This work should provide important information concerning colonization of the human mouth by pioneer bacteria and may demonstrate the ability of SIgA to influence the presence of specific bacterial clones.

口腔和其他粘膜表面的固有微生物群与宿主保持稳态，除非受到干扰、粘膜表面受损或免疫系统受损。 然后，共生细菌能够引起严重的机会性感染。 粘膜表面的适应性体液免疫主要受到分泌性免疫球蛋白 A (SIgA) 的影响，该蛋白被认为在共生细菌的调节中发挥作用。 然而，尽管唾液中含有与共生细菌发生反应的 SIgA 抗体，这些微生物仍会在粘膜和牙齿表面定殖并持续存在。 这表明本土口腔细菌不受粘膜抗体的影响、不受其影响或能够避免粘膜抗体的免疫消除。 这一论点得到了其他人发表的数据的支持，这些数据表明，缺乏粘膜 SIgA 的小鼠及其同窝小鼠的口腔和肠道固有微生物群的获取和组成没有差异，并且共生肠道细菌在小鼠中的定植似乎会产生自限性粘膜免疫反应，导致慢性低反应状态。 在之前的资助期间，我们在一项针对从出生到两岁的人类婴儿的纵向研究中证明，口腔共生细菌 S. mitis biovar 1 会在唾液中诱导有限的抗体反应，与该细菌反应的唾液 SIgA 抗体显示出从出生到两岁的显着下降。 此外，这种细菌表现出广泛的遗传多样性和克隆替代的证据。与此同时，该细菌典型菌株的包膜抗原的蛋白质印迹显示出类似的高度变异性。在这个竞争性的延续中，要测试的假设是，由于克隆替代介导的抗原变异，共生细菌通过诱导有限的唾液 SIgA 抗体反应而在口腔中持续存在。 对出生至 12 个月的婴儿进行纵向研究，具体目标是 (1) 分析从婴儿口腔内脱落表面获得的 S. mitis biovar 1 的克隆多样性，以及 (2) 分析每个婴儿唾液中与其自身 S. mitis biovar 1 分离株发生反应的 SIgA 抗体的多样性。 这项工作应该提供有关先锋细菌在人类口腔定植的重要信息，并可能证明 SIgA 影响特定细菌克隆存在的能力。