Intracerebral infection with murine cytomegalovirus induces CXCL10 and is restricted by adoptive transfer of splenocytes
Intracerebral infection with murine cytomegalovirus induces CXCL10 and is restricted by adoptive transfer of splenocytes
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DOI：
10.1080/13550280490441130
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发表时间：
2004-06-01
影响因子：
3.2
通讯作者：
Lokensgard, JR
中科院分区：
文献类型：
--
作者：
Cheeran, MCJ;Gekker, G;Lokensgard, JR
大脑的内在免疫系统由神经胶质细胞组成，神经胶质细胞对巨细胞病毒（CMV）的刺激产生细胞因子和趋化因子。本实验进行，以确定是否这种内在的神经胶质细胞反应单独是足以控制中枢神经系统（CNS）的CMV感染，或是否还需要来自体细胞免疫系统的效应细胞。将鼠巨细胞病毒（MCMV）立体定向脑室内（icv）注射到免疫活性（C.B-17）小鼠中后，病毒在脑中的传播限于心室壁细胞，并且感染在感染后（p.i.）10天消退。相反，免疫缺陷（C.B-17 SCID/bg）小鼠的icv感染导致病毒从脑室扩散到整个脑实质，这些小鼠死于致命疾病。从主要组织相容性复合体（MHC）匹配，MCMV致敏动物的总脾细胞的连续转移限制了脑内病毒感染到脑室周围细胞，并降低了病毒基因组的报告基因表达水平。外周免疫细胞转移也保护免疫缺陷动物免于致命疾病。从MCMV致敏的脾细胞中去除Thy 1.2（+）细胞可消除过继转移的保护作用。病毒的表达被发现是四倍以上的动物大脑给予Thy 1.2-耗尽的脾细胞比那些接受总未耗尽的细胞。随着MCMV感染在免疫缺陷小鼠的大脑中进行，T细胞趋化因子CXCL 10和CCL 2的水平仍然升高，而接受转移的脾细胞的动物的大脑中CXCL 10水平下降。总之，这些结果证明了T淋巴细胞限制脑内病毒传播的能力，并表明单独的内在胶质细胞反应不足以控制MCMV脑感染。
The brain's intrinsic immune system consists of glial cells that produce cytokines and chemokines in response to stimulation with cytomegalovirus (CMV). The present experiments were undertaken to determine whether this intrinsic glial cell response alone is sufficient to control CMV infection of the central nervous system (CNS) or whether effector cells from the somatic immune system are also required. Following stereotactic, intracerebroventricular (icv), injection of murine cytomegalovirus ( MCMV) into immunocompetent (C.B-17) mice, viral spread in the brain was limited to the cells of the ventricular walls and the infection was resolved by 10 days post infection (p. i.). In contrast, icv infection of immunodeficient (C.B-17 SCID/bg) mice resulted in viral spread from the ventricles throughout the brain parenchyma and these mice succumbed to lethal disease. Adoptive transfer of total splenocytes from major histocompatibility complex (MHC)-matched, MCMV-primed animals restricted intracerebral viral infection to the periventricular cells and reduced levels of reporter gene expression from the viral genome. Peripheral immune cell transfer also protected immunodeficient animals from lethal disease. Depletion of Thy 1.2(+) cells from MCMV-primed splenocytes abolished the protective effect of adoptive transfer. Viral expression was found to be fourfold greater in the brains of animals given Thy 1.2-depleted splenocytes than from those receiving total undepleted cells. As MCMV infection proceeded in the brains of immunodeficient mice, levels of the T-cell chemoattractants CXCL10 and CCL2 remained elevated, whereas CXCL10 levels waned in the brains of animals receiving transferred splenocytes. Taken together, these results demonstrate the ability of T lymphocytes to restrict intracerebral viral spread and indicate that intrinsic glial cell responses alone are insufficient to control MCMV brain infection.