1. Chlamydia trachomatis: TLR4-mediated recognition by human dendritic cells is impaired following oestradiol treatment.
- Author
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Agrawal T, Bhengraj AR, Vats V, and Mittal A
- Subjects
- CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes microbiology, Coculture Techniques, Epithelial Cells cytology, Epithelial Cells immunology, Epithelial Cells microbiology, Estrogens pharmacology, Female, HeLa Cells, Humans, Macrophages immunology, Macrophages microbiology, Signal Transduction immunology, CD4-Positive T-Lymphocytes drug effects, Chlamydia Infections immunology, Chlamydia trachomatis immunology, Estradiol pharmacology, Macrophages drug effects, Toll-Like Receptor 4 immunology
- Abstract
Genital Chlamydia trachomatis infection creates a substantial reproductive health burden in women. The high incidence of asymptomatic infection often precludes timely antibiotic therapy to control the sequelae of infection, and therefore a vaccine is required. Dendritic cells (DC) are now being used as an adjuvant for vaccine development; however, the fate of C. trachomatis in human DC and differential regulation of cytokine secretion remains unclear. Hence, an in vitro study was performed using C. trachomatis (serovar D) elementary body (EB)-pulsed, monocytederived DCs co-cultured with autologous CD4+ T cells. Secreted cytokines were measured to assess the protective/pathogenic immune response. The effect of (beta-oestradiol in the modulation of DC function and on Toll-like receptor (TLR) gene expression was also studied. Elementary body-pulsed DCs showed induction of protective Th1 immune response with upregulation of TLR4 expression, secretion of interleukin (IL)-6, IL-12 and interferon (IFN)-y, together with upregulation of major histocompatibility complex (MHC) class II, CD83 and CD86. When co-cultured with autologous CD4+T cells, DCs presented chlamydial antigens efficiently, as shown by proliferation of T cells and secretion of IL-2 and IFN gamma, which provide a protective immune response. However; pretreatment of cells with oestradiol significantly reduced TLR4 expression and upregulated IL-10 secretion, modulating the Th1 immune response to a Th2-type response, which may lead to pathogenesis.
- Published
- 2013
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