title: NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.
abstract: 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.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.|Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Hofstetter
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Juan A
authors.initials: JA
authors.lastname: De La Cruz
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Weiping
authors.initials: W
authors.lastname: Cao
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Jenish
authors.initials: J
authors.lastname: Patel
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: McCoy
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Justine S
authors.initials: JS
authors.lastname: Liepkalns
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Amoah
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Priya
authors.initials: P
authors.lastname: Ranjan
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Becky A
authors.initials: BA
authors.lastname: Diebold
authors.affiliation: Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Wun-Ju
authors.initials: WJ
authors.lastname: Shieh
authors.affiliation: Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Sherif
authors.initials: S
authors.lastname: Zaki
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: J David
authors.initials: JD
authors.lastname: Lambeth
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000276:immunology*; D000074624:NADPH Oxidase 1; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology*
chemical_list: D023201:CD40 Ligand; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse