NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice

作者：Hofstetter Amelia R; De La Cruz Juan A; Cao Weiping; Patel Jenish; Belser Jessica A; McCoy James; Liepkalns Justine S; Amoah Samuel; Cheng Guangjie; Ranjan Priya; Diebold Becky A; Shieh Wun Ju; Zaki Sherif; Katz Jacqueline M; Sambhara Suryaprakash; Lambeth J David^*; Gangappa Shivaprakash^*

来源：PLos One, 2016, 11(2): e0149864.

DOI：10.1371/journal.pone.0149864

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.

• 出版日期2016-2-24