Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta.

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-alpha/beta (IFN-alpha/beta), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-alpha/beta 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-alpha/beta 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-beta 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-alpha/beta signaling and activation of NK cells in antiviral response of the host.

journal_name

Eur J Immunol

authors

Sato K,Hida S,Takayanagi H,Yokochi T,Kayagaki N,Takeda K,Yagita H,Okumura K,Tanaka N,Taniguchi T,Ogasawara K

doi

10.1002/1521-4141(200111)31:11<3138::aid-immu3138>

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

3138-46

issue

11

eissn

0014-2980

issn

1521-4141

pii

10.1002/1521-4141(200111)31:11<3138::AID-IMMU3138>

journal_volume

31

pub_type

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