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A study of oral streptococci on the dherence and resistance to human immune system and antibacterial agents

口腔链球菌对人体免疫系统和抗菌药物的粘附和耐药性研究

基本信息

批准号：
09671857
负责人：
MIYAKE Yoichiro
金额：
$ 1.98万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671857/
关键词：
streptococci CD15s fosfomycin autoimmunity liver

项目摘要

Streptococcus pyogenes and oral streptococci express CD15s-like antigen which may have a role in pathogenecity of the bacteria. Characterization of the antigen demonstrated the antigen being non-proteinous substance with its molecular size of 400-500 kDa, and contains N-acetylglucosamine, glucose, fructose, galactose, and sialic acid.We investigated the effect of antibiotics on the expression of the antigen by S.pyogenes. Among antibiotics tested, benzylpenicillin, a transpeptidase inhibitor, and fosfomycin reduced the expression of CD15s. It is worth noted that enantiomer fosfomycin, without any antibacterial activity, also reduced the antigen expression.Microorganisms which mimic human antigen, such as Helicobacter pylori and Schistosoma mansonii, induce autoimmune reaction of humans. We injected heat-killed S.intermedius repeatedly to mice from gingiva. As a result, antibody to CD15s was induced and the antibody reacted with mouse neutrophils. In the liver, inflammation occurred and hepatocytes in and around the inflammatory lesion expressed CD15s cytoplasmically. Cell adhesion molecules, E-selectin and ICAM-1 which have a role in infiltration of lymphocytes, were expressed by endothelial cells of central vein and sinusoid. Inflammatory lesion was dominated by lymphocytes while a small number of macrophages were also observed. Most of the infiltrating T cells were CD8+T cells. CD3+T cells and B220+B cells infiltrated in the liver had high binding ability to CD15s-probe. Apoptosis of the hepatocytes in and around inflammatory lesion was demonstrated by TUNEL method. Our results suggest that immunization with CD15s positive S.intermedius from gingiva induced the systemic immune response and trigger autoimmune response in the liver.

化脓性链球菌和口腔链球菌表达CD15s样抗原，可能在细菌的致病过程中起一定作用。该抗原为非蛋白类物质，分子大小为400-500 kDa，含有N-乙酰氨基葡萄糖、葡萄糖、果糖、半乳糖和唾液酸。在接受测试的抗生素中，转肽酶抑制剂青霉素和磷霉素降低了CD15s的表达。值得注意的是，对映体磷霉素没有任何抗菌活性，也降低了抗原的表达。模拟人类抗原的微生物，如幽门螺杆菌和曼氏血吸虫，会诱导人类的自身免疫反应。我们将热灭活的中间链霉菌反复注射到小鼠牙周组织中。结果诱导产生抗CD15s抗体，并与小鼠中性粒细胞发生反应。肝脏出现炎症，炎性病变内及周围肝细胞胞浆表达CD15s。与淋巴细胞浸润有关的细胞黏附分子E-选择素和ICAM-1在中央静脉内皮细胞和肝窦内皮细胞表达。炎性病变以淋巴细胞为主，也可见少量巨噬细胞。浸润性T细胞以CD8+T细胞为主。肝内CD3+T细胞和B220+B细胞与CD15s探针结合能力较强。TUNEL法检测炎性病变内及周围肝细胞的凋亡情况。我们的结果表明，CD15s阳性的中间链霉菌免疫诱导了全身免疫反应，并触发了肝脏的自身免疫反应。