Immune Responses to C. trachomatis Infections in a Non-Human Primate Model

hlamydial infections are the most common bacterial STD in the United States, with an estimated annual incidence of 4 million cases and costs in excess of $2 billion. Pelvic inflammatory disease (PID) (i.e., acute salpingitis) is frequently a consequence of sexually transmitted diseases, including gonococcal, mycoplasmal, and chlamydial infection, and is usually the result of progression of disease from the lower to the upper reproductive tract. Approximately million women are treated for PID in the United States annually, and one-quarter of these women are affected with serious sequelae, including ectopic pregnancy and tubal infertility. As many as half of these PID cases are caused by chlamydiae. Such infections are now recognized as a major public health problem. However, a limited understanding of the immuno-pathogenesis of PID still exists. This has been due in part to the limited number of clinical specimens available for study and the continued need to develop appropriate and suitable animal models in which to study Ch/amydia trachomatis in particular. For the past decade, we have used pig-tailed monkeys to study the pathogenesis of chlamydial cervi-citis and salpingitis. Since the normal reproductive biology of the pig-tailed monkey is well defined, we anticipated that this model would be useful for functional studies following induction of cervicitis and salpingitis and for easily recognizing abnormal morphology in infected animals. Initially, our studies were designed to determine whether the pig-tailed monkey would be an appropriate animal model in which to study the pathogenesis of chla-mydial cervicitis and salpingitis. As described below , the immune responses and histopathologic characteristics of chlamydial infection in this model mimic human cervicitis and salpingitis, although only limited data in humans are available. Thus, we have continued to use the pig-tailed monkey model to evaluate C. trachomatis infection in the lower and upper genital tracts. Seven pig-tailed macaques were inoculated in the cervix with a serovar D strain, while 3 control monkeys were cervically inoculated with uninfected McCoy cells only. The animals that received viable C. tracaomatis were than reinoculated, but only after 2 to 3 consecutive weeks of culture-negative specimens. After spontaneous cessation of cervical shedding of C. trachomatis, repeated inoculation either failed to produce infection or resulted in infection of shorter duration with lower inclusion counts. Thus, the initial cervical infection persisted for 1-15 weeks (average, 9.3 weeks), while reinoculation of the cervix failed in 3 of 7 animals, and among the 4 animals who …