"Herpes simplex virus-1 (HSV-1) is a prevalent and successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After primary lytic replication, it establishes lifelong latency in sensory neurons in the trigeminal ganglion (TG). Recurrent reactivation in the cornea leads to herpetic stromal keratitis (HSK), the leading cause of infectious blindness in developed countries. Neutrophils play a crucial role in managing ocular HSV-1 infections. Yet, the impact of HSV-1 on neutrophil effector function, particularly NET formation or NETosis, remains poorly understood. Our previous studies demonstrated that interferon-λ (IFN-λ) exerts antiviral and immunomodulatory effects against HSV-1-induced corneal pathology and regulates antiviral effectors in neutrophils. In this study, we aim to elucidate the mechanisms by which IFN-λ regulates neutrophil biology to modulate neutrophil extracellular trap (NET) formation (NETosis) and antiviral immunity during corneal HSV-1 infection. Our preliminary data using mouse bone-marrow derived neutrophils suggest that HSV-1 induces NETosis with increased expression of extracellular myeloperoxidase (MPO) and neutrophil elastase (NE) expression. Further, we show that IFN-λ positively regulates HSV-1-induced NETosis to promote anti-viral immunity. Further studies are under investigation to elucidate the molecular mechanisms by which IFN-λ promotes anti-HSV-1 immunity by targeting neutrophils and NETosis.
