Roles of chlamydial lipopoly saccharide and innate immune responses in atherogenesis

衣原体是一种小的专性胞内寄生虫，被归类为革兰氏阴性菌。虽然最近的研究表明肺炎衣原体的慢性炎症反应与动脉粥样硬化的发展有关，但对衣原体诱导宿主细胞激活的机制知之甚少。在衣原体来源的成分中，脂多糖被认为是一种有效的免疫调节剂，衣原体脂多糖具有独特的脂A结构，具有较长但较少的酰基链。在这项研究中，我们利用与肺炎衣原体结构几乎相同的鹦鹉热衣原体内毒素，研究了衣原体内毒素对人PBMC的作用，并与大肠杆菌LPS进行了比较。与大肠杆菌内毒素相似，鹦鹉热衣原体内毒素与单核细胞结合，并以脂多糖结合蛋白(LBP)依赖的方式诱导促炎细胞因子的产生。然而，鹦鹉热肠杆菌脂多糖的效力远低于大肠杆菌…。更多的内毒素结合和细胞因子的产生。有趣的是，鹦鹉热杆菌内毒素的结合是由CD14、TLR4和CD11b介导的，而细胞因子的产生依赖于CD14和TLR4，而不是CD11b。值得注意的是，基于Elis A的结合分析显示鹦鹉热杆菌内毒素直接与LBP和CD14结合，但亲和力远低于大肠杆菌内毒素。综上所述，这些观察结果可能表明，衣原体内毒素与CD14和LBP等内毒素识别分子的结合亲和力较低，对包括单核细胞在内的宿主免疫细胞表现出较弱的生物活性，从而导致感染过程中的慢性(持续性)炎症反应。综上所述，这些观察结果表明，衣原体内毒素与内毒素识别分子的结合亲和力较低，对单核细胞等宿主免疫细胞表现出较弱的生物学活性，从而导致衣原体感染过程中的慢性(持续性)炎症反应。较少

Chlamydiaceae are small obligate intracellular parasites and classified as gram-negative bacteria. Although recent studies have suggested that chronic inflammatory reactions by Chlamydophila pneumoniae is associated with the development of atherosclerosis, little is known about the mechanisms for Chlamydiaceae -induced host cell activation.Among Chlamydiaceae-derived components, LPS is known as a potent immunomodulator, and chlamydial LPS possesses a unique lipid A structure with longer but less acyl chains. In this study, to elucidate the chlamydial LPS-induced immune responses, we evaluated the actions of chlamydial LPS on human PBMC, using Chlamydophila psittaci LPS whose structure is nearly identical to that of C. pneumoniae, and compared with those of E. coli LPS.Similar to E. coli LPS, C. psittaci LPS bound to monocytes and induced the pro-inflammatory cytokine production in an LPS-binding protein (LBP)-dependent manner. However, C. psittaci LPS was much less potent than E. coli … More LPS in both the LPS binding and cytokine production. Interestingly, the binding of C. psittaci LPS was mediated by CD14, TLR4 and CD11b, whereas the cytokine production was dependent on CD14 and TLR4 but not CD11b. Of note, ELIS A-based binding assays revealed that C. psittaci LPS directly bound to LBP and CD14; however the affinities were much less man those of E. coli LPS. Together, these observations possibly suggest that Chlamydiaceae LPS has low binding affinities for LPS-recognition molecules such as CD14 and LBP, and exhibit weak biological activities against host immune cells including monocytes, thereby contributing to the chronic (persistent) inflammatory reactions during infection. Together, these observations indicate that chlamydial LPS has the low binding affinities for LPS-recognition molecules, and exhibits weak biological activities against host immune cells such as monocytes, thereby contributing to the chronic (persistent) inflammatory reactions during chlamydial infection. Less