Tissue Specific Overexpression of Human Heat Shock Protein 70 in Mouse Oviduct Epithelium Reduces Chlamydia Induced Immunopathology

• Published in: The Journal of immunology (1950) Vol. 200; no. 1_Supplement; pp. 114 - 114.20
• Main Authors: Murthy, Ashlesh K., Keeler, Kelly Rae, Do, Jennifer, Seetharaman, Aravind, Ramsey, Kyle H., Ciancio, Mae, Li, weidang
• Format: Journal Article
• Language: English
• Published: 01.05.2018
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.114.20

Abstract Chlamydia trachomatis genital infections lead to severe immunopathological consequences in the upper genital tract (UGT), including pelvic inflammatory disease and infertility, in a small subset of infected women. Heat shock protein 70 (Hsp70) is an evolutionarily conserved stress-induced protein and has been shown to exhibit significant cytoprotective and immunoregulatory activities. However, the role of Hsp70 in genital chlamydial pathologies had not been examined. Hsp70 transgenic (Hsp70 Tg) mice were created by injecting a villin promoter-driven human Hsp70 targeting vector into C57BL/6 oocytes. The villin promoter is active only in the epithelium of the mouse oviduct but not in other parts of the female mouse genital tract. Female, 6-8 week old, Hsp70 Tg and non-transgenic (NTG) littermates were infected intravaginally with 5×104 IFU of C. muridarum. Vaginal chlamydial shedding, bacterial burden in the upper genital tract including oviducts and uterine horns, Chlamydia-specific IFN-γ, TNF-α, and IL-17 production, and serum anti-Chlamydia antibody levels were comparable between NTG and Hsp70 Tg mice. However, at day 80 after inoculation, the incidence and severity of pathology in oviducts, not neighboring uterine horns, was significantly reduced in Hsp70 Tg mice compared to NTG mice. Given the highly polymorphic nature of hsp-70 gene and associated susceptibility to various inflammatory conditions, and the occurrence of immunopathology in only a subset of Chlamydia-infected women, these results also underscore the need to further evaluate the role of hsp-70 in chlamydial immunopathogenesis in the female upper reproductive tract.