NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.
NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.
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DOI：
10.1371/journal.pone.0149864
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Gangappa S
中科院分区：
文献类型：
--
作者：
Hofstetter AR;De La Cruz JA;Cao W;Patel J;Belser JA;McCoy J;Liepkalns JS;Amoah S;Cheng G;Ranjan P;Diebold BA;Shieh WJ;Zaki S;Katz JM;Sambhara S;Lambeth JD;Gangappa S
产生活性氧的NADPH氧化酶家族在甲型流感病毒感染的病理学中的作用仍然是个谜。先前的报道暗示NADPH氧化酶2在甲型流感病毒诱导的炎症中。相比之下，据报道，NADPH氧化酶1（Nox 1）在甲型流感病毒感染后7天内减少小鼠的炎症。然而，NADPH氧化酶1对甲型流感病毒攻击后致死率和适应性免疫的影响尚未研究。在这里，我们报告了与A/PR/8/34甲型流感病毒攻击后的对照组相比，具有催化失活的NADPH氧化酶1（Nox 1 */Y）的小鼠的存活率提高，发病率降低。虽然Nox 1 */Y和对照小鼠之间的肺部炎症变化不明显，但我们观察到感染后第15天T细胞对甲型流感病毒的反应发生了变化，包括Nox 1 */Y的肺和引流淋巴结中表达白细胞介素-7受体的病毒特异性CD 8 + T细胞增加，以及肺和脾中产生精氨酸的T细胞增加。此外，在感染后6天内，来自Nox 1 */Y引流淋巴结的更大百分比的常规和间质树突状细胞表达共刺激配体CD 40。结果表明，NADPH氧化酶1调节对流感病毒感染的先天性和适应性细胞免疫应答，同时也在宿主存活中发挥作用。结果表明，NADPH氧化酶1抑制剂可能是有益的辅助治疗在急性流感感染。
The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection.