Surface Lipoprotein PpiA of Streptococcus mutans Suppresses Scavenger Receptor MARCO-Dependent Phagocytosis by Macrophages
Surface Lipoprotein PpiA of Streptococcus mutans Suppresses Scavenger Receptor MARCO-Dependent Phagocytosis by Macrophages
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DOI：
10.1128/iai.05693-11
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发表时间：
2011-10
影响因子：
3.1
通讯作者：
Tadashi Mukouhara;T. Arimoto;K. Cho;Matsuo Yamamoto;T. Igarashi
中科院分区：
文献类型：
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作者：
Tadashi Mukouhara;T. Arimoto;K. Cho;Matsuo Yamamoto;T. Igarashi
变形链球菌与人类龋齿的发生和发展有关，偶尔从菌血症和感染性心内膜炎患者的血液中分离出来。为了使病原体在受感染的宿主中存活，S.变异体可能在与先天免疫系统的相互作用中发挥重要作用。为了阐明S.变形链球菌在巨噬细胞反应中的作用，我们研究了THP-1衍生的巨噬细胞对变形链球菌的反应。变种人挑战赛Lgt基因的缺失消除了S.变形蛋白，这意味着PpiA是一种脂蛋白，其是通过Lgt锚定在细胞膜中的脂质。人和小鼠腹腔巨噬细胞对ppiA和lgt突变体的吞噬活性均高于野生型，这表明PpiA的存在减少了S.变形菌吞噬作用此外，感染S.在人巨噬细胞中，变形杆菌可显著诱导巨噬细胞胶原结构受体（MARCO）和清道夫受体A（SR-A）的mRNA表达。特别是，MARCO在感染ppiA突变体的人巨噬细胞中的转录和翻译水平高于感染野生型的巨噬细胞。S.在用抗MARCO IgG处理后，人巨噬细胞的变形杆菌显著减少。这些结果表明，S。变形脂蛋白PpiA有助于抑制巨噬细胞对该细菌的MARCO介导的吞噬作用。
ABSTRACT Streptococcus mutans is associated with the initiation and progression of human dental caries and is occasionally isolated from the blood of patients with bacteremia and infective endocarditis. For the pathogen to survive in the infected host, surface lipoproteins of S. mutans are likely to play important roles in interactions with the innate immune system. To clarify the role that a putative lipoprotein, peptidyl-prolyl cis/trans-isomerase (PpiA), of S. mutans plays in the macrophage response, we investigated the response of THP-1-derived macrophages to S. mutans challenge. The deletion of the gene encoding Lgt eliminated PpiA on the cell surface of S. mutans, which implies that PpiA is a lipoprotein that is lipid anchored in the cell membrane by Lgt. Human and murine peritoneal macrophages both showed higher phagocytic activities for the ppiA and lgt mutants than the wild type, which indicates that the presence of PpiA reduces S. mutans phagocytosis. In addition, infection with S. mutans markedly induced mRNAs of macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A) in human macrophages. In particular, transcriptional and translational levels of MARCO in human macrophages infected with the ppiA mutant were higher than those in macrophages infected with the wild type. Phagocytosis of S. mutans by human macrophages markedly decreased after treatment with anti-MARCO IgG. These results demonstrate that the S. mutans lipoprotein PpiA contributes to suppression of MARCO-mediated phagocytosis of this bacterium by macrophages.