Stroke-induced Immunodeficiency Promotes Spontaneous Bacterial Infections and Is Mediated by Sympathetic Activation Reversal by Poststroke T Helper Cell Type 1–like Immunostimulation

TLDR

Infections are a leading cause of death in stroke patients. The study tests whether stroke‑induced immunodeficiency increases susceptibility to bacterial infections. The authors used a mouse model of focal cerebral ischemia to examine this hypothesis. Three days after ischemia, all mice developed septicemia and pneumonia, accompanied by extensive lymphocyte apoptosis and a shift from Th1 to Th2 cytokine production, and adoptive transfer of T and NK cells or IFN‑γ administration markedly reduced bacterial burden, while sympathetic blockade prevented the IFN‑γ defect and lowered mortality, indicating that catecholamine‑mediated lymphocyte dysfunction drives post‑stroke bacterial infections.

Abstract

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-γ–deficient mice, or administration of IFN-γ at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-γ response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the β-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.