Influenza-induced expression of functional tumor necrosis factor-related apoptosis-inducing ligand on human peripheral blood mononuclear cells.
Influenza-induced expression of functional tumor necrosis factor-related apoptosis-inducing ligand on human peripheral blood mononuclear cells.
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DOI：
10.1016/j.humimm.2008.07.012
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发表时间：
2008-10
期刊：
影响因子：
2.7
通讯作者：
Griffith TS
中科院分区：
文献类型：
--
作者：
Brincks EL;Kucaba TA;Legge KL;Griffith TS
与许多其他病毒一样，流感病毒感染的免疫学反应的特点是大量产生促炎细胞因子，包括I型和II型干扰素(IFN)，它们能诱导许多抗病毒作用，并对启动免疫反应的固有和适应性细胞成分至关重要。在这里，我们证明了流感病毒感染诱导了人外周血单个核细胞(PBMC)上功能性TRAIL的表达。与先前检测TRAIL上调的研究一致，在PBMC培养中，TRAIL表达增加与I型和II型干扰素水平增加相关。有趣的是，这些细胞因子的稀释导致TRAIL的表达减少，TRAIL的上调不依赖于活跃的病毒感染，并且在NS-1阴性细胞上观察到TRAIL的表达。此外，流感病毒感染肺腺癌细胞(A549)与未感染的A549相比，对TRAIL诱导的细胞凋亡的敏感度增加。感染的表达TRAIL的PBMC优先杀伤感染的A549细胞，而不影响未感染的细胞，加入可溶性TRAIL-R2：Fc可阻断感染细胞的裂解，表明TRAIL依赖于对感染细胞的杀伤。总之，这些数据表明，TRAIL在原代人类先天免疫细胞和获得性免疫细胞上的表达是对流感感染期间产生的细胞因子的反应，并且在流感病毒感染的细胞中TRAIL的敏感性增加。这些数据还表明，TRAIL是流感刺激的人PBMC用来杀死流感感染的靶细胞的主要机制，并加强了响应TLR激动剂而产生的细胞因子在增强细胞免疫效应功能方面的重要性。
The immunological response to influenza virus infection, like many other viruses, is characterized by robust production of proinflammatory cytokines, including type I and II interferon (IFN), which induce a number of antiviral effects and are essential for priming the innate and adaptive cellular components of the immune response. Here, we demonstrate that influenza virus infection induces the expression of functional TRAIL on human peripheral blood mononuclear cell (PBMC) populations. Consistent with previous studies examining TRAIL upregulation, increased TRAIL expression correlated with increased type I and II IFN levels in PBMC cultures. Interestingly, dilution of these cytokines resulted in decreased expression of TRAIL, TRAIL upregulation was not dependent on active viral infection, and TRAIL was observed on NS-1 negative cells. Furthermore, influenza virus infection of lung adenocarcinoma cells (A549) resulted in increased sensitization to TRAIL-induced apoptosis compared to uninfected A549. Infected PBMC expressing TRAIL preferentially killed infected A549, while not affecting uninfected cells, and the addition of soluble TRAIL-R2:Fc blocked the lysis of infected cells, demonstrating TRAIL-dependent killing of infected cells. Collectively, these data show that TRAIL expression is induced on primary human innate and adaptive immune cells in response to cytokines produced during influenza infection, and that TRAIL-sensitivity is increased in influenza virus-infected cells. These data also suggest that TRAIL is a primary mechanism used by influenza-stimulated human PBMC to kill influenza-infected target cells and reinforce the importance of cytokines produced in response to TLR agonists in enhancing cellular immune effector functions.
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影响因子：
30.5
作者：
Cella, M;Facchetti, F;Colonna, M
通讯作者：
Colonna, M
影响因子：
64.8
作者：
Kash, John C.;Tumpey, Terrence M.;Katze, Michael G.
通讯作者：
Katze, Michael G.
影响因子：
4.4
作者：
Chaperot, L;Blum, A;Plumas, J
通讯作者：
Plumas, J
DOI：
10.1084/jem.190.8.1155
发表时间：
1999-10-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fanger NA;Maliszewski CR;Schooley K;Griffith TS
通讯作者：
Griffith TS
影响因子：
4.4
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G