Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved
Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved
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DOI：
10.1074/jbc.m212829200
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发表时间：
2003-05-02
影响因子：
4.8
通讯作者：
Schumann, RR
中科院分区：
文献类型：
--
作者：
Schröder, NWJ;Morath, S;Schumann, RR
从肺炎链球菌和金黄色葡萄球菌中提取的脂磷壁酸(LTA)分别用氯仿/甲醇法和最近报道的丁醇提取法制备，研究了它与脂多糖结合蛋白(LBP)、CD14、Toll样受体(TLRs)-2和-4以及MD-2的相互作用。来自这两种生物的LTA可诱导人单核巨噬细胞合成细胞因子。活化依赖于LBP和CD14，PhastGel(TM)天然凝胶电泳法证实了LTA与LBP和可溶性CD14形成络合物，以及LBP催化LTA向CD14转移。人胚胎肾(HEK)293/CD14细胞和中国仓鼠卵巢(CHO)细胞只有在转导TLR-2后才对LTA有反应。加入MD-2基因并不影响LTA对这些细胞的刺激作用。我们的数据表明，LTA通过LBP、CD14和TLR-2的天然免疫识别是临床上最重要的革兰氏阳性病原体在感染过程中引起全身并发症的重要机制。然而，排除了TLR-4和AW-2参与这一过程的可能性。
Lipoteichoic acid (LTA) derived from Streptococcus pneumoniae, purified employing a chloroform/methanol protocol, and from Staphylococcus aureus, prepared by the recently described butanol extraction procedure, was investigated regarding its interaction with lipopolysaccharide (LPS)-binding protein (LBP), CD14, Toll-like receptors (TLRs)-2 and -4, and MD-2. LTA from both organisms induced cytokine synthesis in human mononuclear phagocytes. Activation was LBP- and CD14-dependent, and formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis. Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2. Additional transfection with MD-2 did not affect stimulation of these cells by LTA. Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic, complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens. However, the involvement of TLR-4 and AW-2 in this process was ruled out.