Mitochondrial reactive oxygen species modulate innate immune response to influenza A virus in human nasal epithelium.
The innate immune system of the nasal epithelium serves as a first line of defense against invading respiratory viruses including influenza A virus (IAV). Recently, it was verified that interferon (IFN)-related immune responses play a critical role in local antiviral innate immunity. Reactive oxygen species (ROS) generation by exogenous pathogens has also been demonstrated in respiratory epithelial cells and modulation of ROS has been reported to be important for respiratory virus-induced innate immune mechanisms. Passage-2 normal human nasal epithelial (NHNE) cells were inoculated with IAV (WS/33, H1N1) to assess the sources of IAV-induced ROS and the relationship between ROS and IFN-related innate immune responses. Both STAT1 and STAT2 phosphorylation and the mRNA levels of IFN-stimulated genes, including Mx1, 2,5-OAS1, IFIT1, and CXCL10, were induced after IAV infection up to three days post infection. Similarly, we observed that mitochondrial ROS generation increased maximally at 2 days after IAV infection. After suppression of mitochondrial ROS generation, IAV-induced phosphorylation of STAT and mRNA levels of IFN-stimulated genes were attenuated and actually, viral titers of IAV were significantly higher in cases with scavenging ROS. Our findings suggest that mitochondrial ROS might be responsible for controlling IAV infection and may be potential sources of ROS generation, which is required to initiate an innate immune response in NHNE cells.
Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sujin
S
Kim
Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
Min-Ji
MJ
Kim
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Do Yang
DY
Park
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hyo Jin
HJ
Chung
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Chang-Hoon
CH
Kim
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; BK 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
Joo-Heon
JH
Yoon
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: hyunjerry@snu.ac.kr.
Hyun Jik
HJ
Kim
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007372:Interferons / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins / Q000235:genetics; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology*; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000235:genetics; D019562:Viral Load
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D054357:Chemokine CXCL10; C484290:IFIT1 protein, human; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D007372:Interferons
Influenza A virus; Interferon-stimulated genes; Mitochondria; Reactive oxygen species