Institute of Physiology and Pathophysiology, University of Heidelberg, D-69120 Heidelberg, Germany.
Institute of Physiology and Pathophysiology, University of Heidelberg, D-69120 Heidelberg, Germany; Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, D-69120 Heidelberg, Germany.
J Neuroimmunol. 2022 Jul 15;368:577881. doi: 10.1016/j.jneuroim.2022.577881. Epub 2022 Apr 28.
Immunological priming by type II interferon (IFN-γ) is crucial for evoking neurotoxic phenotypes of microglia (tissue-resident macrophages). We report that serial exposure of hippocampal slice cultures to IFN-γ and lipopolysaccharide (Toll-like receptor 4 ligand) induces high release of IL-6, TNF-α and nitric oxide, concomitant loss of electrical network activity (neuronal gamma oscillations) and neurodegeneration. Notably, these effects are still present after 3 days of IFN-γ removal but neither mimicked by IFN-α nor attenuated by anti-inflammatory cytokine, IL-10. Our findings might be relevant for brain diseases featuring elevated IFN-γ levels, such as viral and bacterial infections, multiple sclerosis and Alzheimer's disease.
II 型干扰素（IFN-γ）的免疫启动对于引发小胶质细胞（组织驻留巨噬细胞）的神经毒性表型至关重要。我们报告称，海马切片培养物连续暴露于 IFN-γ 和脂多糖（Toll 样受体 4 配体）会导致 IL-6、TNF-α 和一氧化氮的大量释放，同时丧失电网络活性（神经元γ 振荡）和神经退行性变。值得注意的是，IFN-γ 去除 3 天后这些效应仍然存在，但 IFN-α 不能模拟，抗炎细胞因子 IL-10 也不能减弱。我们的发现可能与具有升高 IFN-γ 水平的脑部疾病有关，例如病毒和细菌感染、多发性硬化症和阿尔茨海默病。
