Ingalls R R, Rice P A, Qureshi N, Takayama K, Lin J S, Golenbock D T
Maxwell Finland Laboratory for Infectious Diseases, Boston City Hospital, Massachusetts, USA.
Infect Immun. 1995 Aug;63(8):3125-30. doi: 10.1128/iai.63.8.3125-3130.1995.
Chlamydia trachomatis is a major etiologic agent of sexually transmitted diseases. Although C. trachomatis is a gram-negative pathogen, chlamydial infections are not generally thought of as endotoxin-mediated diseases. A molecular characterization of the acute immune response to chlamydia, especially with regard to the role of its lipopolysaccharide (LPS), remains to be undertaken. We extracted 15 mg of LPS from 5 x 10(12) C. trachomatis elementary bodies (EB) for analysis of structure and biological activity. When methylated lipid A was subjected to high-pressure liquid chromatography followed by mass spectrometry, the majority of the lipid A was found to be pentaacyl. The endotoxin activities of whole C. trachomatis EB and purified LPS were characterized in comparison with whole Salmonella minnesota R595 and with S. minnesota R595 LPS and lipooligosaccharide from Neisseria gonorrhoeae. Both C. trachomatis LPS and whole EB induced the release of tumor necrosis factor alpha from whole blood ex vivo, and C. trachomatis LPS was capable of inducing the translocation of nuclear factor kappa B in a Chinese hamster ovary fibroblast cell line transfected with the LPS receptor CD14. In both assays, however, C. trachomatis was approximately 100-fold less potent than S. minnesota and N. gonorrhoeae. The observation that C. trachomatis is a weak inducer of the inflammatory cytokine response correlates with the clinical observation that, unlike N. gonorrhoeae infection, genital tract infection with C. trachomatis is often asymptomatic. The ability of specific LPS antagonists to completely inhibit the tumor necrosis factor alpha-inducing activity of whole C. trachomatis EB suggests that the inflammatory cytokine response to chlamydia infection may be mediated primarily through LPS. This implies that the role of other surface protein antigens, at least in terms of eliciting the proinflammatory cytokine response, is likely to be minor.
沙眼衣原体是性传播疾病的主要病原体。尽管沙眼衣原体是革兰氏阴性病原体，但衣原体感染通常不被认为是内毒素介导的疾病。对衣原体急性免疫反应的分子特征进行研究，尤其是关于其脂多糖（LPS）的作用，仍有待开展。我们从5×10¹²个沙眼衣原体原体（EB）中提取了15毫克LPS，用于结构和生物活性分析。当甲基化脂质A进行高压液相色谱分析，随后进行质谱分析时，发现大部分脂质A为五酰基。将沙眼衣原体全EB和纯化的LPS的内毒素活性与明尼苏达沙门氏菌R595全菌、明尼苏达沙门氏菌R595 LPS以及淋病奈瑟菌的脂寡糖进行了比较。沙眼衣原体LPS和全EB均能在体外诱导全血释放肿瘤坏死因子α，并且沙眼衣原体LPS能够在转染了LPS受体CD14的中国仓鼠卵巢成纤维细胞系中诱导核因子κB的转位。然而，在这两种检测中，沙眼衣原体的效力比明尼苏达沙门氏菌和淋病奈瑟菌低约100倍。沙眼衣原体是炎症细胞因子反应的弱诱导剂这一观察结果与临床观察结果相关，即与淋病奈瑟菌感染不同，沙眼衣原体生殖道感染通常无症状。特异性LPS拮抗剂能够完全抑制沙眼衣原体全EB诱导肿瘤坏死因子α的活性，这表明对衣原体感染的炎症细胞因子反应可能主要通过LPS介导。这意味着其他表面蛋白抗原的作用，至少在引发促炎细胞因子反应方面，可能较小。
