TY - JOUR
T1 - Non-apoptotic TRAIL function modulates NK cell activity during viral infection
AU - Cardoso Alves, Ludmila
AU - Berger, Michael D.
AU - Koutsandreas, Thodoris
AU - Kirschke, Nick
AU - Lauer, Christoph
AU - Spörri, Roman
AU - Chatziioannou, Aristotelis
AU - Corazza, Nadia
AU - Krebs, Philippe
N1 - Publisher Copyright:
© 2019 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2020/1/7
Y1 - 2020/1/7
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - IL-15 signaling
KW - NK cells
KW - TNF-related apoptosis-inducing ligand
KW - lymphocytic choriomeningitis virus
UR - http://www.scopus.com/inward/record.url?scp=85075501919&partnerID=8YFLogxK
U2 - 10.15252/embr.201948789
DO - 10.15252/embr.201948789
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C2 - 31742873
AN - SCOPUS:85075501919
SN - 1469-221X
VL - 21
JO - EMBO Reports
JF - EMBO Reports
IS - 1
M1 - e48789
ER -
