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Updated: Nov 4, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection
Tania Lebratti1, Ying Shiang Lim1, Adjoa Cofie1
1Department of Medicine/Division of Infectious Diseases, Washington University School of Medicine, St Louis, United States.
Abstract:
Neutrophil responses against pathogens must be balanced between protection and immunopathology. Factors that determine these outcomes are not well-understood. In a mouse model of genital herpes simplex virus-2 (HSV-2) infection, which results in severe genital inflammation, antibody-mediated neutrophil depletion reduced disease. Comparative single-cell RNA-sequencing analysis of vaginal cells against a model of genital HSV-1 infection, which results in mild inflammation, demonstrated sustained expression of interferon-stimulated genes (ISGs) only after HSV-2 infection primarily within the neutrophil population. Both therapeutic blockade of IFNα/β receptor 1 (IFNAR1) and genetic deletion of IFNAR1 in neutrophils concomitantly decreased HSV-2 genital disease severity and vaginal IL-18 levels. Therapeutic neutralization of IL-18 also diminished genital inflammation, indicating an important role for this cytokine in promoting neutrophil-dependent immunopathology. Our study reveals that sustained type I interferon (IFN) signaling is a driver of pathogenic neutrophil responses and identifies IL-18 as a novel component of disease during genital HSV-2 infection.
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