The research lab of Toni Darville, MD, has studied the pathogenesis of genital tract disease due to Chlamydia trachomatis for many years. Dr. Darville’s research has discovered immune signaling pathways active in disease development, and continue to pursue studies that explore host-pathogen interactions responsible for induction of disease. She is currently working to develop a vaccine to prevent chlamydial infection, and is pursuing genetic and transcriptional microarray studies to determine biomarkers of disease risk and immune pathways that lead to protection from chlamydial infection and disease.
Her lab has successfully used plasmid-deficient attenuated chlamydial strains that do not induce pathology but lead to induction of protective adaptive immune responses, as tools for separating pathogen-specific virulence factors from pathogen-host interactions that drive protection.
Her research is using human blood and genital tract tissue samples collected from women at high risk and followed longitudinally for 12 months to determine chlamydial proteins that induce protective CD4+ Th1 responses. She is examining the role of CD4+ and CD8+ T cells and antibody in protection from ascending infection and from reinfection. Active investigations with human peripheral blood mononuclear cells include determination of T cell clonotypic expansion after repeated infection and HLA-types associated with susceptibility and protection from disease.
She is also examining the role of Th17 cells and T regulatory cells in immunopathogenesis of chlamydial infection using human samples and the mouse model. The development of a chlamydial antigen-specific TCR transgenic mouse provides an excellent tool to advance investigations of the adaptive T cell response to chlamydial infection with the ultimate goal to determine mechanisms to induce protective T cell memory.
Her lab is seeking to identify the local inflammatory and fibrotic pathways most strongly regulated during Chlamydia trachomatis infection utilizing specimens obtained from women with chlamydial pelvic inflammatory disease and women with asymptomatic chlamydial infection. They are also working to identify biomarkers for susceptibility to Chlamydia trachomatis infection and progression to tubal pathology.
In May 2019, Dr. Darville and her collaborators were awarded a five-year, $10.7 million grant from NIAID to establish the UNC Chlamydia Vaccine Initiative STI Cooperative Research Center. The Chlamydia Vaccine Initiative is a partnership of academic institutions and industry to explore systems-level host/pathogen molecular interactions during infection of the female genital tract by C. trachomatis and to develop a vaccine.
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