Chronic stress-induced immunosuppression during Listeria monocytogenes infection

In this study, mice with an intraperitoneal infection with an intracellular parasitic bacterium, Listeria monocytogenes (L. monocytogenes), under repeated cycles of restraint stress (RST) were analyzed to investigate effects of chronic stress on the host defense. We observed that the bacterial infection per se, as well as RST, induced an elevation of endogenous corticosterone levels and RST synergistically enhanced them during the bacterial infection. RST drastically inhibited migration and accumulation of various leukocyte subsets including macrophages, neutrophils, NK cells and lymphocytes at the peritoneal cavity. RST also suppressed the upregulation of the surface expression of class II major histocompatibility complex (MHC) antigen on both peritoneal macrophages and B cells during the bacterial infection. Interestingly, gene expression of iNOS, MCP-1 (JE), and Th1-type cytokines, including IFN-gamma and IL-12, was downregulated in the peritoneal exudate cells (PEC) on day 7 after infection, but that of the Th2-type cytokines (IL-4 and IL-6) was not, indicating that the Th1 immune response is more sensitive to corticosterone than the Th2 immune response. Treatment of the restrained and infected mice with RU-486, a glucocorticoid receptor antagonist, restored the immune responses suppressed by RST to the normal levels, suggesting that the RST-induced elevation of endogenous CORT (corticosterone) levels is a main cause of the immunosuppression during the bacterial infection.