Using Epidemiology, Immunology, and Genomics to Study the Biology of Chlamydia trachomatis

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.