Eeka Prabhakar, Phanithi Prakash Babu
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana State, India.
Neurosci Lett. 2018 Jan 18;664:58-65. doi: 10.1016/j.neulet.2017.11.021. Epub 2017 Nov 10.
Cerebral malaria is a complex, acute, neurological disease characterised by a sudden onset of cerebral symptoms. This disease is manifested as initial arousable stage that is followed by an unarousable coma and eventually death. Parasite burden and CD8+ T cell count in the brain determines the disease outcome. Cytotoxic CD8+ T cell-derived Granzyme-b is required for the development of experimental cerebral malaria (ECM), but the mechanism of pathogenesis is not known. Here, we show that CD8+ T cells infiltrate in to the brain during ECM releasing Granzyme-b that is cytotoxic to neuronal cells. Granzyme-b kills neuronal cells through direct cytotoxicity and also by activating neuronal caspase-3 and calpain1 via cytoskeletal breakdown. Our results showed the increased expression of cell adhesion molecules and chemokine receptors in the brain and their associated infiltration of T cells during ECM.
脑型疟疾是一种复杂的急性神经疾病，其特征为突然出现脑部症状。这种疾病表现为最初的可唤醒阶段，随后进入不可唤醒的昏迷状态，最终导致死亡。脑部的寄生虫负荷和CD8 + T细胞计数决定了疾病的转归。细胞毒性CD8 + T细胞衍生的颗粒酶B是实验性脑型疟疾（ECM）发展所必需的，但发病机制尚不清楚。在这里，我们表明，在ECM期间，CD8 + T细胞浸润到大脑中，释放对神经元细胞具有细胞毒性的颗粒酶B。颗粒酶B通过直接细胞毒性杀死神经元细胞，还通过细胞骨架分解激活神经元半胱天冬酶-3和钙蛋白酶1。我们的结果显示，在ECM期间，大脑中细胞粘附分子和趋化因子受体的表达增加，以及它们相关的T细胞浸润。
