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Non‐apoptotic TRAIL function modulates NK cell activity during viral infection

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Alves Ludmila Cardoso, Berger Michael D, Koutsandreas Thodoris, Kirschke Nick, Lauer Christoph, Spörri Roman, Chatziioannou Aristotelis, Corazza Nadia, Krebs Philippe,
Project mRNA splicing and epithelial integrity
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Original article (peer-reviewed)

Journal EMBO reports
Page(s) e48789
Title of proceedings EMBO reports

Open Access

Type of Open Access Publisher (Gold Open Access)


The role of death receptor signaling for pathogen control and infection-associated pathogenesis is multifaceted and controversial. Here, we show that during viral infection, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) modulates NK cell activity independently of its pro-apoptotic function. In mice infected with lymphocytic choriomeningitis virus (LCMV), Trail deficiency led to improved specific CD8+ T-cell responses, resulting in faster pathogen clearance and reduced liver pathology. Depletion experiments indicated that this effect was mediated by NK cells. Mechanistically, TRAIL expressed by immune cells positively and dose-dependently modulates IL-15 signaling-induced granzyme B production in NK cells, leading to enhanced NK cell-mediated T cell killing. TRAIL also regulates the signaling downstream of IL-15 receptor in human NK cells. In addition, TRAIL restricts NK1.1-triggered IFNg production by NK cells. Our study reveals a hitherto unappreciated immunoregulatory role of TRAIL signaling on NK cells for the granzyme B-dependent elimination of antiviral T cells.