Involvement of lipoprotein PpiA of Streptococcus gordonii in evasion of phagocytosis by macrophages
Involvement of lipoprotein PpiA of Streptococcus gordonii in evasion of phagocytosis by macrophages
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DOI：
10.1111/omi.12031
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发表时间：
2013-10-01
影响因子：
3.7
通讯作者：
Yamamoto, M.
中科院分区：
文献类型：
--
作者：
Cho, K.;Arimoto, T.;Yamamoto, M.
戈登链球菌是一种常见的革兰氏阳性菌，存在于人类口腔中，是感染性心内膜炎(IE)最常见的病因之一。细菌表面分子在IE的建立中起着重要的作用，在IE的建立过程中，戈登氏链球菌的几个蛋白参与了与宿主细胞的结合。在这项研究中，我们鉴定了一种可能的脂蛋白，即肽基-脯氨酰顺/反式异构酶(PpiA)，并阐明了它在巨噬细胞逃避吞噬过程中的作用。编码前脂蛋白二酰甘油转移酶(LGT)基因的减弱改变了PpiA从细胞表面到培养上清液的定位，表明LGT将PpiA固定在细胞膜上。人和小鼠巨噬细胞对ppiA和lgt突变体的吞噬活性均高于野生型，表明ppiA的存在抑制了戈登链霉菌的吞噬作用。经葡聚糖硫酸盐处理的人巨噬细胞对戈登葡萄球菌的吞噬功能明显受损，提示人巨噬细胞A类清道夫受体参与了戈登葡萄球菌的吞噬作用。这些结果证明戈登链球菌脂蛋白PpiA在抑制吞噬细胞吞噬和逃避宿主免疫反应中起重要作用。
Streptococcus gordonii is a commensal grampositive bacterium that resides in the human oral cavity, and is one of the most common causes of infective endocarditis (IE). Bacterial surface molecules play an important role in establishing IE, and several S. gordonii proteins have been implicated in binding to host cells during the establishment of IE. In this study, we identified a putative lipoprotein, peptidyl-prolyl cis/trans isomerase (PpiA), and clarified its role in evasion of phagocytosis by macrophages. Attenuation of the gene encoding prolipoprotein diacylglyceryl transferase (Lgt) altered the localization of PpiA from the cell surface to the culture supernatant, indicating that PpiA is lipid-anchored in the cell membrane by Lgt. Both human and murine macrophages showed higher phagocytic activity towards ppiA and lgt mutants than the wild-type, indicating that the presence of PpiA suppresses phagocytosis of S. gordonii. Human macrophages treated with dextran sulfate had significantly impaired phagocytosis of S. gordonii, suggesting that class A scavenger receptors in human macrophages are involved in the phagocytosis of S. gordonii. These results provide evidence that S. gordonii lipoprotein PpiA plays an important role in inhibiting phagocytic engulfment and in evasion of the host immune response.