Defense against influenza A virus infection: Essential role of the chemokine system
Defense against influenza A virus infection: Essential role of the chemokine system
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DOI：
10.1078/0171-2985-00099
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发表时间：
2001-12-01
期刊：
影响因子：
2.8
通讯作者：
Sprenger, H
中科院分区：
文献类型：
--
作者：
Kaufmann, A;Salentin, R;Sprenger, H
单核/巨噬细胞对甲型流感病毒感染高度敏感。感染后，可检测到新生病毒蛋白合成，但在完成第一个病毒复制周期之前迅速中断。在24-48小时内，感染的单核细胞会因细胞凋亡而死亡。在细胞死亡之前，受感染的单核细胞会启动细胞特异性免疫反应。这包括转录和随后释放肿瘤坏死因子-α(肿瘤坏死因子α)、白介素1β(白介素1β)、白介素6、I型递质和CC趋化因子。细胞因子mRNA的表达增强是由于延长了mRNA的稳定性和基因转录的增强。核因子-kappaB和AP-1等转录因子的激活参与了细胞因子mRNA转录的激活。甲型流感病毒感染单核细胞可诱导单核细胞趋化因子的选择性表达，如MCPA(单核细胞趋化蛋白1)、MIP-α(巨噬细胞炎性蛋白LET)和RANTES(激活后调节，正常T细胞表达和分泌)。与之形成鲜明对比的是，中性粒细胞特异性趋化因子IL-8(白介素8)和Gro-α(生长刺激活性α)的释放完全被抑制。这种差异调节的趋化因子表达可能解释了病毒感染组织的单核细胞浸润性特征。因此，感染甲型流感病毒的单核/巨噬细胞启动了快速的促炎反应，并诱导单核细胞向受感染组织的迁移增加。综上所述，这些机制可能会使受感染的宿主为快速和病毒特异性的免疫反应做好准备。
Monocytes/macrophages are highly susceptible to an infection with influenza A virus. After infection, de novo virus protein synthesis is detectable but rapidly interrupted before completion of the First viral replication cycle. Within 24-48 hours the infected monocytes die by apoptosis. Before cell death, infected monocytes initiate a cell-specific immune response. This includes the transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha), IL-1beta (Interleukin 1beta), IL-6, type I infererons and CC chemokines. Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an augmented gene transcription. Activation of transcription factors such as NF-kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine mRNA transcription. Infection of monocytes with influenza A virus induces the selective expression of mononuclear leukocyte attracting chemokines, such as MCPA (monocyte chemotactic protein 1), MIP-lalpha (macrophage inflammatory protein let) and RANTES (regulated upon activation, normal T cell expressed and secreted). In striking contrast, the release of the neutrophil-specific chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha) is entirely suppressed. This differentially regulated chemokine expression may explain the mononuclear cell infiltrate characteristic for virus-infected tissue. Thus, infection of monocytes/macrophages with influenza A virus primes for a rapid proinflammatory reaction and induces an enhanced immigration of mononuclear cells into infected tissue. Taken together, these mechanisms may prepare the infected host for a fast and virus-specific immune response.