Effects and mechanisms of cold-induced stress on the development of chlamydia genital infection in a mouse model



 DESCRIPTION (provided by applicant): Genital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease (STD) worldwide. If left untreated, chlamydia genital infection leads to complications such as pelvic inflammatory disease, ectopic pregnancy, and infertility. There is an increasing interest in understanding how stress may impact resistance or susceptibility to a number of diseases, including sexually transmitted disease. Many investigators have examined the immune response to C. trachomatis but the effect of stress has not yet been explored. We have demonstrated that prolonged exposure of mice to cold water results in increased intensity of chlamydia genital infection, but the mechanism(s) are not known. Chlamydial immunity is predominantly CD4+ T cell-mediated, and stressors that target T cell differentiation and activation by primary antigen- presenting cells such as dendritic cells are likely to affect immune response against chlamydia infection. The central objective of this proposal is to define the mechanism(s) by which stress may suppress the immune system and increase the intensity of genital C. trachomatis infection and immunopathologies in mice. Our hypothesis is that cold water-induced stress leads to norepinephrine (NE) modulation of immune response to disease sequelae by stimulation of beta-2 adrenergic receptor (β2AR) expression. At present we are against C. trachomatis genital infection by enhancing the production of immunopathogenic cytokines that lead examining in vitro the effect of synthetic NE on the proliferation of different mouse immune cells, including T cells, as measured by cytokine production. In Aim 1 of the proposed project, gene expression of beta adrenergic receptor subtypes on CD4+ T cells will be determined. In Aim 2 the kinetics of cytokines in maturing infection in β2AR-deficient and wild-type mice will be analyzed and compared. Results obtained from this of marrow-derived dendritic cells exposed to NE will be analyzed. In Aim 3, clearance of C. trachomatis genital stress study in mice will provide important new information on the interaction between the immune system and the endocrine system, which could lead to future development of countermeasures and interventions to control chlamydia genital infection and pathologies in human subjects.