LaVerda D, Kalayoglu M V, Byrne G I
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 53706, USA.
Infect Dis Obstet Gynecol. 1999;7(1-2):64-71. doi: 10.1155/S1064744999000137.
The mucosal pathogen Chlamydia trachomatis affects hundreds of millions of people worldwide and is a significant cause of sexually transmitted disease. Although most acute infections can be easily managed, complications often occur that can be especially severe in women. It has been proposed that increased exposure to conserved chlamydial antigens, such as through reinfection or persistent infection, results in chronic inflammation and tissue scarring and contributes to the pathogenesis of endometrial and fallopian tube damage. This immunopathologic damage is believed to be a principal cause of ectopic pregnancy and tubal factor infertility. The chlamydial heat shock protein Hsp60, a homolog of Escherichia coli GroEL, has been identified as one protein capable of eliciting intense mononuclear inflammation. Furthermore, several studies have revealed a correlation between Hsp60 responses and the immunopathologic manifestations of human chlamydial disease. The role of additional antigens in the immunopathologic response to chlamydiae is currently undefined. A prime candidate, however, is the chlamydial GroES homolog Hsp10, which is genetically and physiologically linked to Hsp60. Recent studies provide data to suggest that immune reactivity to Hsp10 is significantly associated with tubal infertility in a chlamydiae-exposed population. Chlamydia pneumoniae is a more recently defined chlamydial species that has been implicated in a variety of ways with chronic disease processes, such as adult onset asthma and atherosclerosis. Evidence indicates that Hsp60 is present in human atheroma and may play a role in lesion development by direct activation of macrophages. Hsp60 causes the elaboration of inflammatory cytokines, the induction of metalloproteinase, and the oxidation of low density lipoprotein. Each of these events is directly associated with the progress of atherosclerosis. Thus, chlamydial heat shock proteins may function in at least two ways to promote chronic disease: first by direct antigenic stimulation and second as signal transducers that result in macrophage activation. These concepts in disease pathology are discussed in the context of chlamydial infections.
黏膜病原体沙眼衣原体在全球感染了数亿人，是性传播疾病的一个重要病因。虽然大多数急性感染易于控制，但并发症经常发生，在女性中可能尤为严重。有人提出，增加对衣原体保守抗原的暴露，如通过再次感染或持续性感染，会导致慢性炎症和组织瘢痕形成，并促使子宫内膜和输卵管损伤的发病机制。这种免疫病理损伤被认为是异位妊娠和输卵管因素不孕的主要原因。衣原体热休克蛋白Hsp60是大肠杆菌GroEL的同源物，已被确定为一种能够引发强烈单核炎症的蛋白。此外，多项研究揭示了Hsp60反应与人类衣原体疾病免疫病理表现之间的相关性。目前尚不清楚其他抗原在衣原体免疫病理反应中的作用。然而，一个主要候选抗原是衣原体GroES同源物Hsp10，它在基因和生理上与Hsp60相关联。最近的研究提供的数据表明，在接触衣原体的人群中，对Hsp10的免疫反应性与输卵管性不孕显著相关。肺炎衣原体是一种最近确定的衣原体物种，已被认为以多种方式与慢性疾病过程有关，如成人哮喘和动脉粥样硬化。有证据表明，Hsp60存在于人类动脉粥样硬化斑块中，可能通过直接激活巨噬细胞在病变发展中发挥作用。Hsp60会引发炎性细胞因子的释放、金属蛋白酶的诱导以及低密度脂蛋白的氧化。这些事件中的每一个都与动脉粥样硬化的进展直接相关。因此，衣原体热休克蛋白可能至少通过两种方式促进慢性疾病：一是通过直接抗原刺激，二是作为导致巨噬细胞激活的信号转导分子。本文在衣原体感染的背景下讨论了这些疾病病理学概念。
