The distinctive features of influenza virus infection of dendritic cells
The distinctive features of influenza virus infection of dendritic cells
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DOI：
10.1016/s0171-2985(98)80078-8
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发表时间：
1998-03-01
期刊：
影响因子：
2.8
通讯作者：
Bhardwaj, N
中科院分区：
文献类型：
--
作者：
Bender, A;Albert, M;Bhardwaj, N
CD8（+）细胞溶解T淋巴细胞（ctl）被认为是抵抗流感病毒感染的关键介质。我们之前已经证明，树突状细胞是抗流感ctl发展的有效抗原呈递细胞。在这里，我们确定了流感病毒与树突状细胞相互作用的独特特征。暴露于流感病毒的树突状细胞在MOIs bf 2-4:1导致> 90%的感染，这表现在病毒蛋白HA和NS1的表达上。感染无毒性，病毒蛋白的表达可持续50 ~ 2天，并保持活力，但很少产生感染性病毒。抗病毒细胞因子ifn - α的大量诱导也发生。流感感染巨噬细胞也导致病毒蛋白在大多数细胞中表达，并合成ifn - α。与树突状细胞相比，巨噬细胞在10-12小时内显示凋亡迹象，大多数细胞在24-36小时内死亡。在这段时间内，巨噬细胞合成的病毒比树突状细胞高10倍，感染的树突状细胞而不是巨噬细胞，可以在缺乏外源性细胞因子（如IL-2）的情况下，诱导纯化血液CD8(+) T细胞产生大量的CTL反应。低水平的感染（moi为0.02）足以产生有效的CTL反应。表达非裂解HA的流感病毒不会引发ctl，这表明病毒必须进入树突状细胞的细胞质才能利用传统的I类加工途径。这些观察结果表明，DCs在处理流感病毒和诱导抗病毒免疫方面是不同的。
CD8(+) cytolytic T lymphocytes (CTLs) are considered to be critical mediators for resistance to influenza virus infection. Me have previously demonstrated that dendritic cells are potent antigen presenting cells in the development of antiinfluenza CTLs. Here we identify distinctive features of the interaction of influenza virus with dendritic cells. Exposure of dendritic cells to influenza virus at MOIs bf 2-4:1 leads to > 90% infection, as manifested by the expression of the viral proteins HA and NS1. The infection is non-toxic as viral protein expression is sustained for > 2 days with retention of viability, but little infectious virus is produced. Substantial induction of the anti-viral cytokine IFN-alpha also occurs. Influenza infection of macrophages also results in viral protein expression in a majority of cells, and synthesis of IFN-alpha. In contrast to dendritic cells, macrophages display evidence of apoptosis within 10-12 hours, and the majority of cells die within 24-36 hours. During this interval macrophages synthesize > 10-fold higher levels of virus than dendritic cells, Infected dendritic cells but not macrophages, can induce substantial CTL responses from purified blood CD8(+) T cells in the absence of exogenous cytokines such as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to generate potent CTL responses. Influenza virus expressing non-cleaved HA does not elicit CTLs indicating that virus must access the cytoplasm of dendritic cells to utilize traditional class I processing pathways. These observations indicate that DCs are distinct in their handling of influenza virus and for the induction of anti-viral immunity.