Ascension Of Chlamydia Is Moderated By Uterine Peristalsis And The Neutrophil Response To Infection

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.Author summary Modelling informs elements of the disease process that are difficult to evaluate due to the complexity and rareness of these factors in human studies. Previous research has led to significant advances in understanding the role of the immune system and pathogen characteristics in the biology of Chlamydia trachomatis. Here 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. Elements of the natural reproductive cycle and immune system were found to be important in moderating the disease process in women.