Natural Killer Cell-Derived Interferon-γ Regulates Macrophage-Mediated Immunopathology During Viral Infection

Regulation of immune responses during viral infection is critical to preventing the development immunopathology that impairs host survival. Natural killer (NK) cells are well known for their antiviral functions that promote viral clearance; however, their roles in limiting immune-mediated pathology are still unclear. Using a mouse model for genital herpes simplex virus type 2 infection, we find that NK cell-derived interferon-gamma directly counteracts interleukin-6-mediated matrix metalloproteases (MMPs) activity in macrophages to limit MMP-mediated tissue damage. Our findings uncover a key immunoregulatory function of NK cells during host-pathogen interactions that highlight the potential of NK cell therapy for treatment of severe viral infections. NK-cell-derived IFN-gamma during viral infection is known to suppress viral replication. Here we show it can suppress IL-6-mediated pathogenic responses in macrophages. These findings highlight the critical role of NK cells in promoting disease tolerance during viral infection.

Automated summary

Regulation of immune responses during viral infection is critical to prevent immunopathology. NK cells not only promote viral clearance but also limit immune-mediated tissue damage. Our study reveals the immunoregulatory function of NK cells in suppressing IL-6-mediated pathogenic responses in macrophages, highlighting the potential of NK cell therapy for severe viral infections.