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Non‐apoptotic TRAIL function modulates NK cell activity during viral infection
Author(s) -
Cardoso Alves Ludmila,
Berger Michael D,
Koutsandreas Thodoris,
Kirschke Nick,
Lauer Christoph,
Spörri Roman,
Chatziioannou Aristotelis,
Corazza Nadia,
Krebs Philippe
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948789
Subject(s) - granzyme , granzyme b , lymphocytic choriomeningitis , biology , microbiology and biotechnology , interleukin 21 , immune system , nk 92 , apoptosis , tumor necrosis factor alpha , immunology , t cell , perforin , cd8 , biochemistry
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 CD 8 + 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 NK 1.1‐triggered IFN γ 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.