Abstract
Chlamydia trachomatis is a common sexually transmitted infection that is associated with a range of serious reproductive tract sequelae including in women Pelvic Inflammatory Disease (PID), tubal factor infertility, and ectopic pregnancy. Ascension of the pathogen beyond the cervix and into the upper reproductive tract is thought to be necessary for these pathologies. However, Chlamydia trachomatis does not encode a mechanism for movement on its genome, and so the processes that facilitate ascension have not been elucidated. Here, we evaluate the factors that may influence chlamydial ascension in women. We constructed a mathematical model based on a set of stochastic dynamics to elucidate the moderating factors that might influence ascension of infections in the first month of an infection. In the simulations conducted from the stochastic model, 36% of infections ascended, but only 9% had more than 1000 bacteria ascend. The results of the simulations indicated that infectious load and the peristaltic contractions moderate ascension and are inter-related in impact. Smaller initial loads were much more likely to ascend. Ascension was found to be dependent on the neutrophil response. Overall, our results indicate that infectious load, menstrual cycle timing, and the neutrophil response are critical factors in chlamydial ascension in women.
Highlights
There is considerable evidence to indicate that Chlamydia trachomatis is one of the aetiological agents responsible for Pelvic Inflammatory Disease (PID), and that women who experience PID are more likely to experience tubal factor infertility and ectopic pregnancy [1,2,3,4]
We combine this body of knowledge to build a model that allows us to understand how and when Chlamydia trachomatis might progress to the upper reproductive tract in women
The findings from this study suggested that innate immune cells contribute to the control of ascending infection, such that the immune response for high infectious loads of bacteria was sufficient to prevent ascension into the upper genital tract, but not so for lower loads
Summary
There is considerable evidence to indicate that Chlamydia trachomatis is one of the aetiological agents responsible for Pelvic Inflammatory Disease (PID), and that women who experience PID are more likely to experience tubal factor infertility and ectopic pregnancy [1,2,3,4]. It is suggested that the development of tubal pathology is a result of a chlamydial infection ascending into the upper reproductive tract combined with a damaging pro-inflammatory response to the pathogen [6]. This study found the response of immune cells (innate and adaptive) was independent of location (lower or upper genital tract) for the relationship with infecting load. The findings from this study suggested that innate immune cells contribute to the control of ascending infection, such that the immune response for high infectious loads of bacteria was sufficient to prevent ascension into the upper genital tract, but not so for lower loads
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