Noradrenergic Neurons Regulate Monocyte Trafficking and Mortality during Gram-Negative Peritonitis in Mice

摘要: Effective host defense requires a robust, yet self-limited response to pathogens. A poorly calibrated can lead either bacterial dissemination due insufficient inflammation or organ injury excessive inflammation. Recent evidence suggests that the cholinergic anti-inflammatory reflex helps calibrate immune response. However, influence of peripheral noradrenergic neurons, which are primarily sympathetic in regulating immunity remains incompletely characterized. Using model 6-hydroxydopamine-mediated nerve ablation, we show elimination neurons improves survival during Klebsiella pneumoniae peritonitis (67 versus 23%, p < 0.005) mice. The benefit results from enhanced MCP-1-dependent monocyte recruitment and subsequent decrease loads. Splenectomy eliminated both 6-hydroxydopamine recruitment, suggesting monocytes recruited peritoneum originate spleen. These suggest regulate through two pathways. First, nerve-derived norepinephrine directly restrains MCP-1 production by peritoneal macrophages infection. Second, derived vagally innervated splenic regulates egress. Removal these modulators enhances antibacterial survival. may have implications for how states catecholamine excess infections.