Plasmid-Deficient Chlamydia muridarum Fail to Induce Immune Pathology and Protect against Oviduct Disease

• Published in: Journal of Immunology Vol. 179; no. 6; pp. 4027 - 4034
• Main Authors: O'Connell, Catherine M, Ingalls, Robin R, Andrews, Charles W., Jr, Scurlock, Amy M, Darville, Toni
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2007
• Subjects: Animals; Cell Line; Cell Line, Transformed; Chlamydia Infections - immunology; Chlamydia Infections - pathology; Chlamydia Infections - prevention & control; Chlamydia muridarum - classification; Chlamydia muridarum - genetics; Chlamydia muridarum - immunology; Chlamydia trachomatis; Epitopes, T-Lymphocyte - immunology; Fallopian Tubes - immunology; Fallopian Tubes - microbiology; Fallopian Tubes - pathology; Female; Genital Diseases, Female - immunology; Genital Diseases, Female - pathology; Genital Diseases, Female - prevention & control; Humans; Immunity, Innate; Immunization, Secondary; Mice; Mice, Inbred C3H; Phenotype; Plasmids - genetics; Plasmids - immunology; Signal Transduction - immunology; Th1 Cells - immunology; Th1 Cells - microbiology; Toll-Like Receptor 2 - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.6.4027

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the world. In women, genital infection can cause endometritis and pelvic inflammatory disease with the severe sequelae of ectopic pregnancy or infertility. Chlamydia sp. do not damage tissues directly, but induce an injurious host inflammatory response at the infected site. In the murine model of genital disease with Chlamydia muridarum, TLR2 plays a role in both early production of inflammatory mediators and development of chronic oviduct pathology. We report the results of studies with plasmid-cured C. muridarum mutants that retain the ability to infect the murine genital tract, but fail to cause disease in the oviduct. These mutants do not stimulate TLR2-dependent cytokine production in mice, nor in innate immune cells or epithelial cells in vitro. They induce an effective Th1 immune response, with no evidence for Th1-immune-mediated collateral tissue damage. Furthermore, mice previously infected with the plasmid-deficient strains are protected against oviduct disease upon challenge with virulent C. muridarum. If plasmid-cured derivatives of human C. trachomatis biovars exhibit similar phenotypic characteristics, they have the potential to serve as vaccines to prevent human disease.