Innate immune response of human alveolar macrophages during influenza A infection.
Innate immune response of human alveolar macrophages during influenza A infection.
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DOI：
10.1371/journal.pone.0029879
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mason RJ
中科院分区：
文献类型：
--
作者：
Wang J;Nikrad MP;Travanty EA;Zhou B;Phang T;Gao B;Alford T;Ito Y;Nahreini P;Hartshorn K;Wentworth D;Dinarello CA;Mason RJ
肺泡巨噬细胞（AM）是肺中启动对流感病毒的炎症和免疫反应的关键细胞类型之一。然而，AM中流感感染引起的全基因组变化尚未确定。我们使用Affytelium HG-U133 Plus 2.0芯片对H1N1甲型流感病毒PR/8应答的人AM进行了基因分析，并通过实时RT-PCR和ELISA验证了mRNA和蛋白水平的变化。我们用当代H3 N2流感病毒A/纽约/238/2005（NY/238）证实了应答。为了了解局部细胞反应，我们还评估了旁分泌因子对病毒诱导的趋化因子和细胞因子分泌的影响。此外，我们研究了PR/8感染后巨噬细胞受体表达和病原体摄取的变化。虽然巨噬细胞不能释放大量的感染性病毒，我们观察到一个强大的诱导I型和III型干扰素和几种细胞因子和趋化因子流感感染后。CXCL 9、10和11是流感感染最高度诱导的趋化因子。紫外线灭活废除病毒诱导的细胞因子和趋化因子的反应，与CXCL 10的例外。当代流感病毒NY/238感染AM诱导了与PR/8相似的反应。抑制TNF和/或IL-1β活性可显著降低促炎趋化因子CCL 5和CXCL 8的分泌，降幅超过50%。PR/8感染还显著降低巨噬细胞受体的mRNA水平，包括C型凝集素结构域家族7成员A（CLEC 7A）、巨噬细胞清道夫受体1（MSR 1）和CD 36，并降低酵母聚糖的摄取。总之，流感感染诱导了广泛的促炎症反应，在人类AM。靶向先天免疫反应的局部组分可能提供一种控制体内甲型流感感染诱导的促炎反应的策略。
Alveolar macrophages (AM) are one of the key cell types for initiating inflammatory and immune responses to influenza virus in the lung. However, the genome-wide changes in response to influenza infection in AM have not been defined. We performed gene profiling of human AM in response to H1N1 influenza A virus PR/8 using Affymetrix HG-U133 Plus 2.0 chips and verified the changes at both mRNA and protein levels by real-time RT-PCR and ELISA. We confirmed the response with a contemporary H3N2 influenza virus A/New York/238/2005 (NY/238). To understand the local cellular response, we also evaluated the impact of paracrine factors on virus-induced chemokine and cytokine secretion. In addition, we investigated the changes in the expression of macrophage receptors and uptake of pathogens after PR/8 infection. Although macrophages fail to release a large amount of infectious virus, we observed a robust induction of type I and type III interferons and several cytokines and chemokines following influenza infection. CXCL9, 10, and 11 were the most highly induced chemokines by influenza infection. UV-inactivation abolished virus-induced cytokine and chemokine response, with the exception of CXCL10. The contemporary influenza virus NY/238 infection of AM induced a similar response as PR/8. Inhibition of TNF and/or IL-1β activity significantly decreased the secretion of the proinflammatory chemokines CCL5 and CXCL8 by over 50%. PR/8 infection also significantly decreased mRNA levels of macrophage receptors including C-type lectin domain family 7 member A (CLEC7A), macrophage scavenger receptor 1 (MSR1), and CD36, and reduced uptake of zymosan. In conclusion, influenza infection induced an extensive proinflammatory response in human AM. Targeting local components of innate immune response might provide a strategy for controlling influenza A infection-induced proinflammatory response in vivo.
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1152/ajplung.00388.2007
发表时间：
2008-06-01
影响因子：
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作者：
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