Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β

Kojiro Sato, Shigeaki Hida, Hiroshi Takayanagi, Taeko Yokochi, Nobuhiko Kayagaki, Kazuyoshi Takeda, Hideo Yagita, Ko Okumura, Nobuyuki Tanaka, Tadatsugu Taniguchi, Kouetsu Ogasawara

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Natural killer (NK) cells play an important role in early defense against viral infection. The cytotoxic activity of NK cells is increased by interferon-α/β (IFN-α/β), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-α/β contribute to the NK-cell-mediated antiviral response is not well understood. Here we provide evidence that the cytotoxicity of NK cells is enhanced by IFN-α/β through induction of TNF-related apoptosis-inducing ligand (TRAIL). Isolation and analysis of the murine TRAIL promoter revealed the presence of an IFN-stimulated response element (ISRE), which binds to the transcription factor ISGF3 (interferon stimulated gene factor-3). This promoter is indeed activated by IFN-β in ISGF3-dependent manner. We also show that virally infected cells, but not uninfected cells, are susceptible to TRAIL-mediated cytotoxicity in vitro, and that the TRAIL expressed in NK cells is indeed crucial in limiting virus replication in vivo. Thus, our study reveals a new molecular link between IFN-α/β signaling and activation of NK cells in antiviral response of the host.

Original languageEnglish
Pages (from-to)3138-3146
Number of pages9
JournalEuropean Journal of Immunology
Volume31
Issue number11
DOIs
Publication statusPublished - 2001 Dec 11
Externally publishedYes

Keywords

  • Encephalomyocarditis virus
  • NK cell
  • TRAIL
  • Type I IFN

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sato, K., Hida, S., Takayanagi, H., Yokochi, T., Kayagaki, N., Takeda, K., Yagita, H., Okumura, K., Tanaka, N., Taniguchi, T., & Ogasawara, K. (2001). Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β. European Journal of Immunology, 31(11), 3138-3146. https://doi.org/10.1002/1521-4141(200111)31:11<3138::AID-IMMU3138>3.0.CO;2-B