Roles of chlamydial lipopoly saccharide and innate immune responses in atherogenesis

衣原体科是小的专性细胞内寄生虫，属革兰氏阴性菌。尽管最近的研究表明肺炎衣原菌的慢性炎症反应与动脉粥样硬化的发展有关，但对衣原菌诱导的宿主细胞活化的机制知之甚少。在衣原体衍生的成分中，LPS被认为是一种有效的免疫调节剂，衣原体LPS具有独特的脂质a结构，具有较长的酰基链，但酰基链较少。在本研究中，为了阐明衣原体LPS诱导的免疫应答，我们使用结构与肺炎链球菌几乎相同的裸鼻衣原体LPS，并与大肠杆菌LPS进行比较，评估衣原体LPS对人PBMC的作用。与大肠杆菌LPS相似，鹦鹉螺杆菌LPS与单核细胞结合，以LPS结合蛋白（LBP）依赖的方式诱导促炎细胞因子的产生。然而，鹦鹉螺脂多糖的结合和细胞因子的产生都比大肠杆菌强。有趣的是，猕猴桃脂多糖的结合是由CD14、TLR4和CD11b介导的，而细胞因子的产生依赖于CD14和TLR4，而不依赖于CD11b。值得注意的是，基于ELIS的结合实验显示，鹦鹉螺脂多糖直接结合LBP和CD14；但与大肠杆菌LPS的亲和性要小得多。总之，这些观察结果可能表明，衣原科LPS对CD14和LBP等LPS识别分子的结合亲和力较低，对宿主免疫细胞（包括单核细胞）的生物活性较弱，从而导致感染期间的慢性（持续性）炎症反应。总之，这些观察结果表明，衣原体LPS对LPS识别分子的结合亲和力较低，对宿主免疫细胞（如单核细胞）的生物活性较弱，从而导致衣原体感染期间的慢性（持续）炎症反应。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