Characterization of immune cells of stressed beta2-adrenergic receptor homozygous knockout mouse model during Chlamydia muridarum genital infection

Abstract

Abstract The relationship of stress in chlamydia genital disease pathogenesis and its influence on the host immune response remains unknown. Beta2-adrenergic receptor(β2-AR), the major receptor of the stress hormone norepinephrine (NE), is known to impair the function of immune cells. This study was undertaken to determine whether cold-induced stress (CIS) results in differential viability percent of immune cells β2-AR KO and WT C57BL/6J treated with NE, β2-AR agonist(Fenoterol), or antagonist(ICI 118,551), and patterns of cytokine production. CIS was induced by immersing mice in cold water for five minutes daily for 21 days. Total CD4+, CD8+, differentiated bone marrow-derived monocytes were purified by negative selection and treated with chemicals for one hour before proliferation for 48 h proliferation. The vi-cell viability analyzer showed that NE results in a 30 and 40 % decrease in viability of WT C57BL/6J CD4+ T and CD8+ cells, respectively, compared to KO (p<0.05). Similarly, NE and Fenoterol resulted in a 20 and 27% decrease in viability of bone marrow-derived monocytes compared to the β2-AR KO mice. Cells treated with ICI 118, 551 showed the slightest reduction in viability (12%) compared to those treated with NE. ELISA results show decreased IL-4 and increased IFN-g secretion by CD4+ T cells of β2-AR KO compared to WT. The secretion of TNF-a by CD8+ cells and bone marrow cells treated with NE and β2-AR agonist or antagonist was high in all treatment groups. This study provides insights for the first time to better understand the NE-β2-AR pathway during chlamydia genital infection. Supported by WV-INBRE of NIH Grant P20GM103434 and NIH grant # 1R15AI124156-01 given to BSC.