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

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Death receptor signaling plays a complex role in controlling infections and causing disease.
• The specific functions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in viral infections are not fully understood.

Purpose of the Study:

• To investigate the role of TRAIL in modulating natural killer (NK) cell activity during viral infection.
• To elucidate the mechanisms by which TRAIL influences immune responses and pathogenesis.

Main Methods:

• Utilized a mouse model infected with lymphocytic choriomeningitis virus (LCMV).
• Examined the impact of Trail deficiency on CD8+ T-cell responses, NK cell activity, and viral clearance.
• Investigated TRAIL's modulation of IL-15 signaling and granzyme B production in NK cells.
• Assessed TRAIL's effect on IFNγ production in NK cells.

Main Results:

• Mice lacking Trail exhibited enhanced CD8+ T-cell responses, leading to faster viral clearance and reduced liver pathology.
• NK cells were identified as the primary mediators of this protective effect.
• TRAIL was found to positively modulate IL-15 signaling-induced granzyme B production in NK cells, promoting T-cell killing.
• TRAIL was also shown to restrict NK1.1-triggered IFNγ production by NK cells.

Conclusions:

• TRAIL signaling on NK cells plays a significant immunoregulatory role during viral infections.
• TRAIL enhances NK cell-mediated killing of T cells via granzyme B, impacting viral control and pathogenesis.
• This study uncovers a novel function of TRAIL in regulating antiviral T-cell populations.