Jeffries Austin M, Marriott Ian
Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA.
Neurosci Lett. 2017 Sep 29;658:53-56. doi: 10.1016/j.neulet.2017.08.039. Epub 2017 Aug 19.
While microglia and astrocytes are known to produce key inflammatory and anti-viral mediators following infection with replicative DNA viruses, the mechanisms by which these cell types perceive such threats are poorly understood. Recently, cyclic GMP-AMP synthase (cGAS) has been identified as an important cytosolic sensor for DNA viruses and retroviruses in peripheral leukocytes. Here we confirm the ability of human microglial and astrocytic cell lines and primary human glia to respond to foreign intracellular double stranded DNA. Importantly, we provide the first demonstration that human microglia and astrocytes show robust levels of cGAS protein expression at rest and following activation. Furthermore, we show these cell types also constitutively express the critical downstream cGAS adaptor protein, stimulator of interferon genes (STING). The present finding that human glia express the principle components of the cGAS-STING pathway provides a foundation for future studies to investigate the relative importance of these molecules in clinically relevant viral CNS infections.
虽然已知小胶质细胞和星形胶质细胞在感染复制性DNA病毒后会产生关键的炎症和抗病毒介质，但这些细胞类型感知此类威胁的机制却知之甚少。最近，环状GMP-AMP合酶（cGAS）已被确定为外周白细胞中DNA病毒和逆转录病毒的重要胞质传感器。在这里，我们证实了人类小胶质细胞系、星形胶质细胞系以及原代人类胶质细胞对外源细胞内双链DNA作出反应的能力。重要的是，我们首次证明，人类小胶质细胞和星形胶质细胞在静息状态和激活后均显示出强大水平的cGAS蛋白表达。此外，我们表明这些细胞类型还组成性地表达关键的下游cGAS衔接蛋白——干扰素基因刺激物（STING）。人类胶质细胞表达cGAS-STING途径的主要成分这一发现为未来研究这些分子在临床相关病毒性中枢神经系统感染中的相对重要性奠定了基础。
