The induction of pattern-recognition receptor expression against influenza a virus through Duox2-derived reactive oxygen species in nasal mucosa

Hyun Jik Kim, Chang Hoon Kim, Min Ji Kim, Ji Hwan Ryu, Sang Yeop Seong, Sujin Kim, Su Jin Lim, Michael J. Holtzman, Joo Heon Yoon

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Westudied the relative roles ofDuox2-derived reactive oxygen species (ROS) in host defense against influenza A virus (IAV) infection in normal human nasal epithelial cells and mouse nasal mucosa.We found thatDuox2 primarily generatedROS rapidly after IAVinfection in normal human nasal epithelial 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 (RIG)-I and melanoma differentiation-associated protein 5 (MDA5) transcription. After intranasal IAV inoculation into mice, viral infection was significantly aggravated from 3 days postinoculation (dpi) in the nasal mucosa, and the IAVviral titer was highest at 7 dpi.BothRIG-I andMDA5messenger RNA 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 messenger RNA levels were induced to a lower extent in the nasal mucosa of the mice that were inoculated with Duox2 short hairpin RNA, 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 andMDA5to resist IAV infection in human nasal epithelium and mouse nasal mucosa.

Original languageEnglish
Pages (from-to)525-535
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number4
DOIs
Publication statusPublished - 2015 Oct 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'The induction of pattern-recognition receptor expression against influenza a virus through Duox2-derived reactive oxygen species in nasal mucosa'. Together they form a unique fingerprint.

  • Cite this