Abstract
Chronic psychological stress has been shown to adversely impact immune system functions and compromise host defenses against various infections. However, the underlying mechanisms remain elusive. Recent studies have demonstrated that myeloid-derived suppressor cells (MDSCs) play an important role in regulating immunity. It is of interest to explore whether or not chronic psychological stress plays immunosuppressive functions partially by inducing MDSCs accumulation. In this work, we report that chronic psychological stress led to the accumulation of CD11b+Gr1+ cells in the bone marrow of BALB/c mice. Repeated β-agonist infusion showed no such effect. However, β-adrenergic blockade, but not glucocorticoids blockade, partially reversed the accumulation of CD11b+Gr1+ cells under the condition of chronic psychological stress, suggesting catecholamines collaborate with other factors to induce the accumulation. Further exploration indicates that cyclooxygenase 2 (COX-2)-prostaglandin E2 (PGE2) loop might act downstream to induce the accumulation. A majority of the accumulated CD11b+Gr1+ cells were Ly6G+Ly6Clow immature neutrophils, which inhibited cytokine release of macrophages as well as T cell responsiveness. Moreover, the accumulated CD11b+Gr1+ cells under the condition of chronic psychological stress expressed multiple inhibitory molecules. Taken together, our data demonstrate for the first time that chronic psychological stress induces MDSCs accumulation in mice, which can contribute to immunosuppression.
Highlights
More and more demands and stimuli continuously enhance people’s psychological stress level
Despite that recent studies have shown the reduction of various effectors and/or a functional compromise of such effectors caused by increased plasma levels of endogenous glucocorticoids and catecholamines mediate the immunosuppressive effects of chronic psychological stress [2,3,13,14], the pathogenic mechanisms underlying the negative impact of chronic psychological stress on host defenses against infection remain elusive
Elevated levels of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) in tumor microenvironment have been identified to induce the expansion of myeloid-derived suppressor cells (MDSCs) [19,20,21] Over the last few years, it has become appreciated that MDSCs participate in a variety of inflammatory immune responses and accumulate in spleens of mice in various models of immunosuppression [22,23]
Summary
More and more demands and stimuli continuously enhance people’s psychological stress level. Despite that recent studies have shown the reduction of various effectors and/or a functional compromise of such effectors caused by increased plasma levels of endogenous glucocorticoids and catecholamines mediate the immunosuppressive effects of chronic psychological stress [2,3,13,14], the pathogenic mechanisms underlying the negative impact of chronic psychological stress on host defenses against infection remain elusive. Elevated levels of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) in tumor microenvironment have been identified to induce the expansion of MDSCs [19,20,21] Over the last few years, it has become appreciated that MDSCs participate in a variety of inflammatory immune responses and accumulate in spleens of mice in various models of immunosuppression [22,23]. We investigated the relationship between psychological stress and MDSCs, and found that chronic psychological stress leads to the accumulation of PMNMDSCs in the bone marrow of BALB/c mice
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