Assessment of Transcription Factors and Cytokines of CD4+ T Cells in beta2-Adrenergic Receptor Deficient Stressed Mice during Chlamydia Infection 2260245

Abstract

Abstract Introduction Genital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. However, the relationship between stress, chlamydia genital disease, and its influence on the host immune response remains unknown. It is reported that the beta2-adrenergic receptor (β2-AR) expressed on immune cells is the target of the stress hormone, norepinephrine, during stress. Previously, we demonstrated that cold-induced stress (CIS) enhances the severity of chlamydia genital infection in mice by downregulating T-bet gene expression and interferon-gamma (IFN-γ) production, while upregulating GATA-3 gene expression and the secretion patterns of Thelper cytokines. However, the roles of Thelper17 and Tregulatory cells are unknown in our stress model. Methods This study aimed to determine the cytokine production by CD4+ T cells and the gene expression profiles of transcription factors, retinoic acid-related orphan receptor γt (RORγt) and FoxP3, using quantitative PCR and ELISA. Chronic stress was produced by immersing mice in cold water for 5 minutes daily over 21 days. Results Decreased gene expression of RORγt and FoxP3 was observed in β2-AR KO stressed mice compared to stressed mice (P < 0.05). Furthermore, the secretion of IFN-γ, interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, and IL-23 was high in CD4+ cells of β2-AR knockout (KO) mice compared to that of stressed wildtype (P < 0.05). Moreover, differential expressions of surface markers of naïve, effector, and memory cells of stress and non-stress mice were observed. Conclusion The obtained data show that a deficiency in β2-AR leads to the restoration of protective immune responses in stressed mice. The animal model study may give insight into how to control the effect of stress on the high prevalence of chlamydia in the low socioeconomic status population. Funding Source WV-INBRE P20GM103434 and NIH grant #R15AI172169 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)