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Duox2-derived Reactive Oxygen Species Induce Pattern Recognition Receptors' Expression Against Influenza A Virus in Nasal Mucosa

tetano

Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2015 Mar 9. [Epub ahead of print]
[h=1]Duox2-derived Reactive Oxygen Species Induce Pattern Recognition Receptors' Expression Against Influenza A Virus in Nasal Mucosa.[/h] Kim HJ[SUP]1[/SUP], Kim CH, Kim MJ, Ryu JH, Seong SY, Kim S, Lim SJ, Holtzman MJ, Yoon JH.
[h=3]Author information[/h]

[h=3]Abstract[/h] We studied the relative roles of Duox2-derived reactive oxygen species (ROS) in host defense against influenza A virus (IAV) infection in normal human nasal epithelial (NHNE) cells and mouse nasal mucosa. We found that Duox2 primarily generated ROS rapidly after IAV infection in NHNE cells, and that knockdown of Duox2 aggravated IAV infection. In addition, Duox2-derived ROS enhancement significantly suppressed IAV infection in nasal epithelium. In particular, Duox2-derived ROS were required for the induction of retinoic acid-inducible gene 1 (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) transcription. Following intranasal IAV inoculation into mice, viral infection was significantly aggravated from 3 days post-infection (dpi) in the nasal mucosa and the IAV viral titer was highest at 7 dpi. Both RIG-I and MDA5 mRNA levels increased dominantly in mouse nasal mucosa from 3 dpi; consistent with this, RIG-I and MDA5 proteins were also induced after IAV infection. RIG-I and MDA5 mRNA levels were induced to a lower extent in the nasal mucosa of the mice which were inoculated Duox2 shRNA and the IAV viral titer was significantly higher in nasal lavage. Taken together, Duox2-derived ROS are necessary for the innate immune response and trigger the induction of RIG-I and MDA5 to resist IAV infection in human nasal epithelium and mouse nasal mucosa.


[h=4]KEYWORDS:[/h] Duox2; Influenza A virus; MDA5; RIG-I; Reactive oxygen species

PMID: 25751630 [PubMed - as supplied by publisher]
 
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