| First Author | Lebratti T | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34047696 | Mgi Jnum | J:308492 |
| Mgi Id | MGI:6728244 | Doi | 10.7554/eLife.65762 |
| Citation | Lebratti T, et al. (2021) A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection. Elife 10:e65762 |
| abstractText | 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 IFNalpha/beta 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. |
