title: Reactive oxygen species delay control of lymphocytic choriomeningitis virus.
abstract: Cluster of differentiation (CD)8(+) T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8(+) T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1(-/-)) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage.
authors: Institute of Experimental Immunology, University Hospital of Zurich, Schmelzbergstrasse 12, Zurich 8091, Switzerland.
authors: P A
authors: PA
authors: Lang
authors: H C
authors: HC
authors: Xu
authors: M
authors: M
authors: Grusdat
authors: D R
authors: DR
authors: McIlwain
authors: A A
authors: AA
authors: Pandyra
authors: I S
authors: IS
authors: Harris
authors: N
authors: N
authors: Shaabani
authors: N
authors: N
authors: Honke
authors: S Kumar
authors: SK
authors: Maney
authors: E
authors: E
authors: Lang
authors: V I
authors: VI
authors: Pozdeev
authors: M
authors: M
authors: Recher
authors: B
authors: B
authors: Odermatt
authors: D
authors: D
authors: Brenner
authors: D
authors: D
authors: Häussinger
authors: P S
authors: PS
authors: Ohashi
authors: H
authors: H
authors: Hengartner
authors: R M
authors: RM
authors: Zinkernagel
authors: T W
authors: TW
authors: Mak
authors: K S
authors: KS
authors: Lang
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione