title: Chlamydia trachomatis: TLR4-mediated recognition by human dendritic cells is impaired following oestradiol treatment.
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.
authors.affiliation: National Institute of Pathology, Indian Council of Medical Research (ICMR), New Delhi, India.
authors.forename: T
authors.initials: T
authors.lastname: Agrawal
authors.forename: A R
authors.initials: AR
authors.lastname: Bhengraj
authors.forename: V
authors.initials: V
authors.lastname: Vats
authors.forename: A
authors.initials: A
authors.lastname: Mittal
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D004967:Estrogens; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004958:Estradiol