Chlamydia infections are a cause of blindness worldwide and a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. Our application will examine fundemental aspects of protective CD4 T cells during infection of the female reproductive tract mucosa. Our experimental approach is unique in that it utilizes a natural route of infection, uses an established model where CD4 T cells participate in bacterial clearance, and allows for direct visualization of endogenous Chlamydia-specific CD4 T cells using reagents that were recently developed in our laboratory. Our application specifically proposes to, (i) examine CD4 T cell heterogeneity and the contribution of these heterogeneous responses to protection and pathology, (ii) examine whether antibiotic-treatment adversely affects the development of protective TRM cells in the reproductive tract mucosa, (iii) determine whether the use of flagellin can enhance moderate protective immunity elicited by the single antigen PmpG1. Understanding each of these issues will increase our knowledge of Chlamydia-specific CD4 T cell biology and may be vitally important for the generation of a new Chlamydia vaccine.
The CDC estimates that Chlamydia is one of the most prevalent bacterial infections in the US and causes upper reproductive tract pathology in a growing number of otherwise health young women. Unfortunately, women with untreated Chlamydia infection can develop serious pelvic inflammatory disease (PID), infertility, chronic pelvic pain, or suffer from ectopic pregnancy. Given the high incidence of infection and the potential for serious pathology, the current consensus among scientists and clinicians is that an effective Chlamydia vaccine is needed. In order for a vaccine to be generated, greater understanding of host immunity to Chlamydia infection in the upper reproductive tract is required. Our application will utilize new antigen-specific reagents that we have recently generated for the mouse model of genital Chlamydia infection. We will use these reagents to examine the heterogeneity of the CD4 T cell response to infection, the affect of antibiotic treatment on developing immunity, and boosting protective immunity to infection.
