Institute of Biomedicine of Seville (IBIS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41012 Seville, Spain.
Department of Medical Physiology and Biophysics, Faculty of Medicine, University of Seville, 41009 Sevilla, Spain.
Cells. 2020 Jul 17;9(7):1717. doi: 10.3390/cells9071717.
The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.
小胶质细胞引发的促炎免疫反应是几种神经退行性疾病发病机制的关键因素。尽管小胶质细胞的研究已经有一个多世纪的历史，但过去二十年的研究使我们的理解呈指数级增长。在这里，我们讨论了由特定配体与模式识别受体（包括 Toll 样受体 4 (TLR4) 或髓样细胞表达的触发受体 2 (TREM2)）结合或促炎信号通路（如半胱天冬酶介导的免疫反应）触发的从稳态小胶质细胞向反应性小胶质细胞的表型转化。此外，新的研究学科，如表观遗传学和免疫代谢，为我们提供了一个更全面的视角，了解 DNA 甲基化、microRNAs 和代谢组学的变化如何影响促炎反应。本综述旨在从不同角度讨论我们目前对促炎小胶质细胞的认识，包括最近的研究亮点，如外泌体在神经炎症传播中的作用，以及小胶质细胞研究中的新兴技术，包括正电子发射断层扫描 (PET) 扫描和使用诱导多能干细胞 (iPSCs) 产生的人小胶质细胞。最后，我们还讨论了促炎小胶质细胞在神经退行性疾病中的作用的当前思路。
