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

Abstract

Regulation of immune responses during viral infection is critical to preventing the development immunopathology that impairs host survival. 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-IFN-γ directly counteracts IL-6 mediated matrix metalloproteases (MMP) 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.