Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, An der Lutter 24, 37075, Göttingen, Germany.
J Neuroinflammation. 2018 Jun 7;15(1):175. doi: 10.1186/s12974-018-1209-2.
Bacterial meningitis is associated with high mortality and long-term neurological sequelae. Increasing the phagocytic activity of microglia could improve the resistance of the CNS against infections. We studied the influence of activin A, a member of the TGF-β family with known immunoregulatory and neuroprotective effects, on the functions of microglial cells in vitro.
Primary murine microglial cells were treated with activin A (0.13 ng/ml-13 μg/ml) alone or in combination with agonists of TLR2, 4, and 9. Phagocytosis of Escherichia coli K1 as well as release of TNF-α, IL-6, CXCL1, and NO was assessed.
Activin A dose-dependently enhanced the phagocytosis of Escherichia coli K1 by microglial cells activated by agonists of TLR2, 4, and 9 without further increasing NO and proinflammatory cytokine release. Cell viability of microglial cells was not affected by activin A.
Priming of microglial cells with activin A could increase the elimination of bacteria in bacterial CNS infections. This preventive strategy could improve the resistance of the brain to infections, particularly in elderly and immunocompromised patients.
细菌性脑膜炎与高死亡率和长期神经后遗症有关。增加小胶质细胞的吞噬活性可以提高中枢神经系统对感染的抵抗力。我们研究了激活素 A（TGF-β 家族的一个成员，具有已知的免疫调节和神经保护作用）对体外小胶质细胞功能的影响。
用激活素 A（0.13ng/ml-13μg/ml）单独或与 TLR2、4 和 9 的激动剂联合处理原代小鼠小胶质细胞。评估大肠杆菌 K1 的吞噬作用以及 TNF-α、IL-6、CXCL1 和 NO 的释放。
激活素 A 剂量依赖性地增强了 TLR2、4 和 9 的激动剂激活的小胶质细胞对大肠杆菌 K1 的吞噬作用，而不会进一步增加 NO 和促炎细胞因子的释放。激活素 A 对小胶质细胞的细胞活力没有影响。
用激活素 A 对小胶质细胞进行预处理可以增加细菌性中枢神经系统感染中细菌的清除。这种预防策略可以提高大脑对感染的抵抗力，特别是在老年和免疫功能低下的患者中。
