Saturday, May 10, 2025
5/10/2025
Enhancing memory T cell defense in the female reproductive tract. - Abstract The sexually transmitted pathogen Chlamydia trachomatis (C. trachomatis) is the most common sexually transmitted infection (STI) and the costliest bacterial STI. Furthermore, STI incidence and prevalence studies estimate that women bare the highest burden of C. trachomatis infections in the United States. These infections often progress undetected and can ascend from the vaginal mucosa into the upper reproductive tract leading to severe health complications, including infertility, chronic pelvic pain, and ectopic pregnancies. Moreover, these infections can increase the risk of acquiring more severe secondary infections, including Neisseria gonorrhoeae (N. gonorrhoeae), antimicrobial-resistant strains (AMR), and Human Immunodeficiency Virus type 1 (HIV-1). Memory T cells that become localized in the female reproductive tract (FRT) mucosa through recent infection or vaccination in animal models have been shown to provide optimal immune protection from C. trachomatis, leading to more rapid pathogen clearance and reducing disease severity. Therefore, generating memory T cells against bacterial STIs in the FRT is a promising approach to enhancing cellular immunity. Previous scientific investigations into understanding memory T cell longevity outside the circulation demonstrate that environmental signals provided by the tissues provide critical support required for their homeostasis and survival in the lung, skin, and gut. Yet, despite the fact that chlamydial reinfections in women are common and there is no available vaccine, we have a very limited perspective on how the tissue environment of the FRT impacts T cell-mediated immunity generated against STIs. Therefore, a major challenge for developing strategies, including vaccine designs that can prevent bacterial STIs, including chlamydial infections in women, is to determine how we can support long-lived and durable immunity in the FRT under menstrual cycle regulation. Our proposal aims to understand the mechanism(s) driving the survival and recall of resident memory T cells (TRM) localized in the FRT following a previous infection.
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