Investigating the role of repeated low-dose infections in Chlamydia pathogenesis.

Chlamydia is the leading cause of sexually transmitted bacterial infections and the most common cause of infectious blindness worldwide. Rates of Chlamydia infection are increasing steadily worldwide, including in Canada and the US. Despite this demonstrated and growing impact on human health, there is currently no vaccine against Chlamydia. A key component of vaccine research is to have reliable animal models that can mimic closely human infection and disease processes. The symptoms of Chlamydia infection are often subtle or absent. As most people are unaware of their infection until they are tested or develop complications such as infertility, Chlamydia infections are commonly transmitted between sex partners in a series of repeated low-dose infections (RLDIs). However, conventional mouse models use a single high-dose of infection. Importantly, Chlamydia infection in mice, but not humans, protects against reinfection, raising a question as to whether we are using an appropriate animal model for studying Chlamydia and for vaccine research. My laboratory has recently developed a new mouse model of RLDIs to mimic closely the nature of infections in humans. We have acquired multiple lines of evidence to show that a single high-dose infection and RLDIs induce different types of immune responses and degrees of tissue damage, with the most severe tissue damage occurring with RLDIs. The proposed research will use this newly developed RLDIs mouse model to investigate the immune responses and immunological mechanisms involved in each step of the disease. The results of this research will advance greatly our understanding of the Chlamydia-induced disease process. Our study has a strong potential to translate the design and evaluation of vaccines and novel therapies from animal model to humans. Our work can also be applied to understanding other infectious diseases.