Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii
Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii
复制标题
DOI：
10.1128/iai.01042-10
复制
发表时间：
2011-08-01
影响因子：
3.1
通讯作者：
Barragan, Antonio
中科院分区：
文献类型：
--
作者：
Dellacasa-Lindberg, Isabel;Fuks, Jonas M.;Barragan, Antonio
在中枢神经系统（CNS）播散性弓形虫病往往伴随着致命的后果。对感染鼠模型的研究集中在系统免疫在控制弓形虫脑炎中的作用，而对CNS中具有免疫功能的常驻细胞的贡献的认识仍然有限。在这项研究中，神经胶质细胞的作用是解决在设置复发弓形虫感染小鼠。在脑实质中原位复制寄生虫的病灶附近观察到活化的星形胶质细胞和小胶质细胞。用弓形虫速殖子体外感染原代小胶质细胞和星形胶质细胞。小胶质细胞允许寄生虫复制，感染的小胶质细胞很容易穿过transwell膜和细胞单层。因此，受感染的小胶质细胞，而不是星形胶质细胞，表现出高运动性表型，让人想起最近描述的受感染的树突状细胞。与γ干扰素激活的小胶质细胞相反，弓形虫感染的小胶质细胞没有上调主要组织相容性复合体（MHC）II类分子和共刺激分子CD86。然而，弓形虫感染的小胶质细胞和星形胶质细胞表现出对T细胞介导的杀伤的敏感性增加，导致体外寄生虫快速转移到效应T细胞。我们推测，胶质细胞和T细胞，除了它们在触发抗寄生虫免疫的作用，也可能作为“特洛伊木马”，矛盾地促进传播的弓形虫在中枢神经系统内。据我们所知，这是第一次报告的迁移激活的居民中枢神经系统细胞的细胞内寄生虫。
Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome. Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites in situ in the brain parenchyma. Toxoplasma gondii tachyzoites were allowed to infect primary microglia and astrocytes in vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia, Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet Toxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells in vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as "Trojan horses," paradoxically facilitating dissemination of Toxoplasma within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.