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

Ludmila Cardoso Alves, Michael D. Berger, Thodoris Koutsandreas, Nick Kirschke, Christoph Lauer, Roman Spörri, Aristotelis Chatziioannou, Nadia Corazza, Philippe Krebs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 IFNγ 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.

Original languageAmerican English
Article numbere48789
JournalEMBO Reports
Volume21
Issue number1
DOIs
StatePublished - 7 Jan 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

  • CD8 T cells
  • IL-15 signaling
  • NK cells
  • TNF-related apoptosis-inducing ligand
  • lymphocytic choriomeningitis virus

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