From the Department of Medicine, University of British Columbia; and Vaccine Research Laboratory, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.
Sex Transm Dis. 2021 May 1;48(5):319-322. doi: 10.1097/OLQ.0000000000001316.
The traditional framework in which to study the biology of human infectious diseases involves characterizing interactions and features of the host, pathogen, and environment. Using the tools of epidemiology, immunology, and genomics allows one to study the biology of infectious disease within this framework. The study of Chlamydia trachomatis biology vividly illustrates the usefulness for the approach. I note key findings from my own studies on C. trachomatis epidemiology, immunology, and genomics to show how important light has been shed on its biology and how this has impacted the Chlamydia field generally. In particular, the epidemiology of C. trachomatis diseases in women shows its impact on reproduction and how public health programs to detect and treat infection has reduced that impact but at the cost of arresting the development of protective immunity and increasing the risk of infection and reinfection. Immunological studies demonstrate the importance of CD4 Th1 cells in protection and that antibiotic treatment interferes with the development of protective immunity when given early in the course of infection. Evaluating the T-cell antigen landscape for C. trachomatis and Chlamydia muridarum demonstrates the role of surface proteins such as the major outer-membrane protein and the polymorphic membrane proteins as major protective CD4 T-cell antigens. Genomic studies reveal that the genome of organism has 3 loci of immunological interest. The antigen loci of the major outer-membrane protein and polymorphic membrane proteins are hotspots for both mutation and recombination, and the plasticity zone contains immune evasion genes that are highly variable from species to species. Interestingly, these 3 loci seem to have entered the Chlamydia phylum at the time of the evolution of the Chlamydiaceae when they became pathogens of vertebrates and encountered the adaptive immune system. In aggregate, these 3 approaches have shed light on human C. trachomatis infections and suggest paths for vaccine development. These approaches are likely to remain useful for the further study of C. trachomatis and for other human pathogens.
传统的研究人类传染病生物学的框架包括描述宿主、病原体和环境的相互作用和特征。利用流行病学、免疫学和基因组学的工具可以在这个框架内研究传染病的生物学。沙眼衣原体生物学的研究生动地说明了这种方法的有用性。我注意到我自己在沙眼衣原体流行病学、免疫学和基因组学研究中的关键发现，以展示它的生物学是如何被揭示的，以及这对一般的衣原体领域产生了怎样的影响。特别是，女性沙眼衣原体疾病的流行病学表明了它对生殖的影响，以及发现和治疗感染的公共卫生计划如何降低了这种影响，但代价是阻止了保护性免疫的发展，并增加了感染和再感染的风险。免疫研究表明 CD4 Th1 细胞在保护中的重要性，并且抗生素治疗在感染过程的早期给予时会干扰保护性免疫的发展。评估沙眼衣原体和鼠衣原体的 T 细胞抗原景观表明，表面蛋白如主要外膜蛋白和多态膜蛋白作为主要的保护性 CD4 T 细胞抗原的重要作用。基因组研究揭示了该生物体的基因组有 3 个具有免疫意义的基因座。主要外膜蛋白和多态膜蛋白的抗原基因座是突变和重组的热点，而可塑性区包含逃避免疫的基因，这些基因在物种间高度多样化。有趣的是，这 3 个基因座似乎在衣原体科进化时进入了衣原体门，当时它们成为了脊椎动物的病原体，并遇到了适应性免疫系统。总的来说，这 3 种方法揭示了人类沙眼衣原体感染的情况，并为疫苗开发提出了途径。这些方法很可能仍然有助于进一步研究沙眼衣原体和其他人类病原体。
