Altered myeloid and lymphoid immune cell responses following repeated social defeat stress

Dysregulation of the innate immune response has frequently been described in stress-associated psychiatric disorders such as major depressive disorder (MDD). However the kinetics and cellular origin of cytokine and chemokine expression are not well understood. Aim of this study was to elucidate stress-induced changes in the immune response in mice. After 2, 6, or 10 daily social defeats, mice were tested for social interaction, expression levels of immune-related genes were assessed in brain and spleen tissues, and splenocytes and mononuclear cells isolated from the brain were analyzed by flow cytometry. Mice that developed social avoidance showed a decreased expression of genes encoding C-C chemokines accompanied by a reduction in the percentages of activated T lymphocytes and reduced IFN-γ expression levels in the spleens of defeated mice. Also, diminished percentages of CD4+FoxP3+ regulatory T cells (Treg) and lower TGF-beta mRNA levels accumulated in the spleens of these animals. In contrast, enhanced percentages of CD45hiCD11b+ cells representing peripheral myeloid cells immigrated into the brain of defeated animals. In summary, stress induced social avoidance was accompanied by an altered expression of CC chemokine genes and reduced T cell activation in the spleen, associated with an increased brain invasion of myeloid cells. Further studies will address the underlying molecular mechanisms, the cell types involved, and the immune cell phenotype in patients with MDD. This study was supported by Innovative Medizinische Forschung (IMF AM211307)