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

Cardoso Alves, Ludmila; Berger, Michael; Koutsandreas, Thodoris; Kirschke, Nick; Lauer, Christoph; Spörri, Roman; Chatziioannou, Aristotelis; Corazza, Nadia; Krebs, Philippe (2020). Non-apoptotic TRAIL function modulates NK cell activity during viral infection. EMBO reports, 21(1), e48789. EMBO Press 10.15252/embr.201948789

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Cardoso Alves, Ludmila; Berger, Michael; Kirschke, Nick; Lauer, Christoph; Corazza, Nadia and Krebs, Philippe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1469-221X

Publisher:

EMBO Press

Language:

English

Submitter:

Philippe Krebs

Date Deposited:

21 Nov 2019 14:30

Last Modified:

09 Jan 2020 01:32

Publisher DOI:

10.15252/embr.201948789

Related URLs:

PubMed ID:

31742873

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.135404

URI:

https://boris.unibe.ch/id/eprint/135404

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