Characterization of physiological and neural alterations in chlamydial reproductive tract infection

Chlamydia trachomatis infection is the most reported sexually transmitted infection worldwide. It is one of the major causes of pelvic inflammatory disease that accounts for many gynaecological problems such as ectopic pregnancy, chronic pelvic pain, and infertility. While much effort has been invested in understanding the immunological aspect of this infection, this thesis focuses on two different aspects – (i) the physiological and (ii) the neuroimmunological aspects. Chapter 1 lays the fundamental understanding of Chlamydia reproductive tract infection and explicates the idea formation and rationale of this thesis. It narrates through the evoked immunological responses and describes the link of this to possible physiological and neuroimmunological alterations in Chlamydia infections. Chapter 2 consolidates all the materials and methods employed in this thesis. It covers the detailed description of experimental methods to how the results were analysed in this thesis. Images were also included for better visualisation and understanding. Chapter 3 is a published chapter that focuses on the physiological alterations caused by Chlamydia infection. It is the first study thus far to explore the physiological functions of non-pregnant uterine and cervical tissues during Chlamydia infection. Different infection timepoints were incorporated to allow a greater level of insight into the impact of infection stages on reproductive tract physiology. Chapter 4 focuses on the neuroimmunological alteration in the spinal cord during Chlamydia infection. This is an extension from Chapter 3 and therefore, the impact of infection timepoints on neuroinflammation were also characterized. This study is the first to examine possible neuroinflammation in Chlamydia infection, and perhaps in sexually transmitted infection to date. Chapter 5 explores the effects of anti-cytokine therapy in resolving peripheral inflammation, oviduct pathology, and neuroinflammation caused by Chlamydia infection. It simultaneously compares the outcomes with antibiotic treatment which acted as a control in the experimental design. In addition, the potential of antibiotic treatment in resolving neuroinflammation was also explored in this chapter. Chapter 6 discusses the application of the findings in a broader sense. This chapter also identifies the limitations and strengths of this thesis. Future directions that can be extended from this thesis are also discussed. Lastly, it finishes with the overall conclusion that further emphasizes the highlights of this thesis.