tetano
Editor, Senior Moderator
PLoS One. 2016 Feb 24;11(2):e0149864. doi: 10.1371/journal.pone.0149864. eCollection 2016.
[h=1]NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.[/h] Hofstetter AR[SUP]1,[/SUP][SUP]2[/SUP], De La Cruz JA[SUP]1[/SUP], Cao W[SUP]1[/SUP], Patel J[SUP]1[/SUP], Belser JA[SUP]1[/SUP], McCoy J[SUP]2[/SUP], Liepkalns JS[SUP]1[/SUP], Amoah S[SUP]1[/SUP], Cheng G[SUP]2[/SUP], Ranjan P[SUP]1[/SUP], Diebold BA[SUP]2[/SUP], Shieh WJ[SUP]3[/SUP], Zaki S[SUP]3[/SUP], Katz JM[SUP]1[/SUP], Sambhara S[SUP]1[/SUP], Lambeth JD[SUP]2[/SUP], Gangappa S[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 26910342 [PubMed - in process]
[h=1]NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.[/h] Hofstetter AR[SUP]1,[/SUP][SUP]2[/SUP], De La Cruz JA[SUP]1[/SUP], Cao W[SUP]1[/SUP], Patel J[SUP]1[/SUP], Belser JA[SUP]1[/SUP], McCoy J[SUP]2[/SUP], Liepkalns JS[SUP]1[/SUP], Amoah S[SUP]1[/SUP], Cheng G[SUP]2[/SUP], Ranjan P[SUP]1[/SUP], Diebold BA[SUP]2[/SUP], Shieh WJ[SUP]3[/SUP], Zaki S[SUP]3[/SUP], Katz JM[SUP]1[/SUP], Sambhara S[SUP]1[/SUP], Lambeth JD[SUP]2[/SUP], Gangappa S[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 26910342 [PubMed - in process]