Mitochondria-derived reactive oxygen species negatively regulates immune innate signaling pathways triggered by a DNA virus, but not by an RNA virus.
Reactive oxygen species (ROS) are crucial secondary messengers of signaling pathways. Redox-dependent signaling events have been previously described in the innate immune response. However, the mechanism by which ROS modulates anti-viral innate immune signaling is not fully clarified. Here, we report that mitochondria-derived ROS differentially regulate the innate response to DNA and RNA viruses (herpes simplex virus (HSV) and Sendai virus (SeV), respectively), with the cytokine response to HSV being negatively regulated by mitochondrial ROS. Importantly, specific activation of Toll-like receptors (TLRs) and DNA receptors (DNARs) but not retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), led to signaling cascades that were inhibited by mitochondrial ROS production. Thus, localized mitochondrial ROS exerts negative modulation of innate immune responses to the DNA virus HSV-2 but not the RNA virus SeV.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Regina
R
Gonzalez-Dosal
Kristy A
KA
Horan
Søren R
SR
Paludan
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012367:RNA, Viral / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D029082:Sendai virus / Q000276:immunology*; D015398:Signal Transduction
D016207:Cytokines; C033365:DNA receptor; D004279:DNA, Viral; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D012367:RNA, Viral; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases