Lebratti, Tania, Lim, Ying Shiang, Cofie, Adjoa, Andhey, Prabhakar, Jiang, Xiaoping, Scott, Jason, Fabbrizi, Maria Rita 
ORCID: 0000-0002-5156-1575, Ozanturk, Ayse Naz, Pham, Christine, Clemens, Regina et al (show 3 more authors)
(2021)
A sustained type I IFN-neutrophil-IL-18 axis drives pathology during mucosal viral infection.
ELIFE, 10.
e65762-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Vagina, Mucous Membrane, Neutrophils, Vero Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Herpesvirus 1, Human, Herpesvirus 2, Human, Herpes Genitalis, Disease Models, Animal, Interferon Type I, Interleukin-18, Antibodies, Signal Transduction, Immunity, Mucosal, Neutrophil Activation, Female, Receptor, Interferon alpha-beta, Host-Pathogen Interactions, Chlorocebus aethiops |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Jan 2022 09:33 |
| Last Modified: | 09 Mar 2024 02:59 |
| DOI: | 10.7554/eLife.65762 |
| Open Access URL: | https://elifesciences.org/articles/65762 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147094 |
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