Treponemal phospholipids inhibit innate immune responses induced by pathogen-associated molecular patterns
Treponemal phospholipids inhibit innate immune responses induced by pathogen-associated molecular patterns
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DOI：
10.1074/jbc.m306735200
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发表时间：
2003-11-07
影响因子：
4.8
通讯作者：
Ogawa, T
中科院分区：
文献类型：
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作者：
Hashimoto, M;Asai, Y;Ogawa, T
宿主对微生物组分的先天免疫应答，称为病原体相关分子模式（PAMP），由细胞受体和血清蛋白调节和修饰，包括Toll样受体（TLR）、CD 14和LPS结合蛋白（LBP）。我们证明了密螺旋体膜脂质抑制PAMPs诱导的免疫反应。脂质的化学结构被阐明为磷脂酰甘油（PG）衍生物，这是稀缺的，在大多数哺乳动物组织，但相对丰富的密螺旋体膜脂质。天然和合成PG对应物以及相关天然阴离子磷脂、磷脂酰肌醇、磷脂酰丝氨酸和心磷脂也表现出抑制作用。此外，我们注意到PG通过阻断PAMPs与LBP和CD 14的结合来抑制PAMPs诱导的免疫应答。此外，PG降低LPS注射小鼠血清中促炎细胞因子的产生，并抑制感染密螺旋体的小鼠脓肿形成。这些结果表明，密螺旋体磷脂干扰LBP/CD 14的功能，并作为先天性免疫反应的调节剂。
Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol ( PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses.