Chronic psychological stress induces the accumulation of myeloid-derived suppressor cells in mice

PLoS One. 2013 Sep 18;8(9):e74497. doi: 10.1371/journal.pone.0074497. eCollection 2013.

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+Ly6C(low) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / metabolism
  • Catecholamines / metabolism
  • Cell Count
  • Chronic Disease
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology*
  • Organ Size
  • Restraint, Physical
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology*

Substances

  • CD11b Antigen
  • Catecholamines
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (31270960, 31100544), the National Key Technologies R&D Program for New Drugs (2013ZX09103003-010), and National Key Basic Research Program of China (2010CB911904). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.