The study for the immune evasion of developing cerebral neurons infected with cytomegaloviurs

本文研究了MCMV感染C57 BL/6小鼠脑发育过程中NK细胞和脑巨噬细胞来源的NO引起的先天性免疫应答的作用。接种MCMV的新生小鼠脑的病毒滴度（LD 50的一半）在感染后7天（dpi）达到峰值，然后下降。新生小鼠脑中的病毒复制通过施用抗脱唾液酸-GM 1抗体（NK细胞的特异性抑制剂）或L-N6-（1-亚氨基乙基）-赖氨酸（NO2的特异性抑制剂）而显著增强。因此，NK细胞和NO有助于从脑中清除病毒。在感染的早期阶段（3dpi），在侧脑室（V）的细胞中检测到MCMV E1抗原阳性细胞和病毒DNA。注射后7 d，E1阳性细胞不仅见于侧脑室的细胞，而且见于海马（Hp）和皮质（Cx）的神经元。感染后11天，E1阳性细胞从心室壁消失，但在感染后11天，E1阳性细胞从心室壁消失。 ...更多信息 在神经元中（图6A）。在7 dpi时，在心室壁中，GM 1（NK细胞标记物）、NOS（巨噬细胞标记物）显著表达，而在海马中，虽然E1抗原在神经元中表达，但NK细胞和巨噬细胞的标记物几乎不表达。病毒DNA在海马的神经元中也几乎检测不到。推测来自心室壁感染细胞的一些信号激活NK细胞和巨噬细胞。来自NK细胞的INF可以诱导巨噬细胞中的NOS，然后来自活化的巨噬细胞的细胞因子如IL 12激活NK细胞，导致感染细胞的裂解。相反，海马神经元中的长期感染可能逃避先天免疫并转移到持续感染。据报道，先天免疫应答开始于NK细胞通过NK细胞的Ly 49 H分子与病毒感染细胞上的MCMV的m157蛋白之间的相互作用识别MCMV感染的细胞。这是可能的m157蛋白作为配体的NK细胞的Ly 49受体的表达可能是不足以在MCMV感染的神经元诱导先天性免疫反应。少

The role of innate immune responses caused by NK cells and NO derived from brain macrophages during MCMV infection in the developing brains of C57BL/6 mice was investigated. The viral titer of the brains of neonatal mice inoculated with MCMV (half of LD50) peaked at 7 days post-infection (dpi) then declined. Viral replication in the brain of newborn mice was significantly enhanced by administration of anti-asialo-GM1 antibody, a specific inhibitor of NK cells, or L- N6-(1-imminoethyl)-lysine, a specific inhibitor of NO2. Thus, NK cells and NO contribute to viral clearance from the brain. At early phases of infection (3 dpi), the MCMV E1 antigen-positive cells and viral DNA were detected in cells of the lateral ventricle (V). At 7 dpi the E1-positive cells were found not only in cells of the lateral ventricle but also in the neurons of the hippocampus (Hp) and cortex (Cx). At a prolonged phase of infection (11 dpi), the E1-positive cells disap- peared from the ventricular wall, but pers … More isted in neurons (Figure 6A). At 7 dpi, in the ventricular wall, a GM1 (NK cell marker), NOS (macrophage marker) were expressed markedly, whereas in the hippocampus, although the E1 antigen was expressed in neurons, the markers of NK cells and macrophages were hardly expressed. Viral DNA was also hardly detected in neurons of the hippocampus.It is hypothesised that some signals from the infected cells in the ventricular walls activate NK cells and macrophages. INF from NK cells may induce NOS in macrophages, then cytokines such as IL12 from the activated macrophages activate NK cells, resulting in lysis of the infected cells. In contrast, the prolonged infected neurons in the hippocampus may evade the innate immunity and transfer to persistent infection. It has been reported that innate immune responses begin with the recognition of MCMV-infected cells by NK cells via the interaction between the Ly49H molecule of NK cells and the m157 protein of MCMV on virus-infected cells. It is possible that expression of m157 proteins as ligands for Ly49 receptor of NK cells may be insufficient in MCMV-infected neurons to induce the innate immune response. Less