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IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1-Induced Corneal Immunopathology
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 206(8)
- Publication Year :
- 2020
-
Abstract
- HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4+ T cell–mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/β) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined. Our study using a mouse model of SK pathogenesis shows that HSV-1 infection induces a robust IFN-λ response compared with type I IFN production at the corneal mucosal surface. However, the normal progression of SK indicates that the endogenous IFN responses are insufficient to suppress HSV-1–induced corneal pathology. Therefore, we examined the therapeutic efficacy of exogenous rIFN-λ during SK progression. Our results show that rIFN-λ therapy suppressed inflammatory cell infiltration in the cornea and significantly reduced the SK pathologic condition. Early rIFN-λ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1β, and CXCL-1 production in the cornea. Notably, the virucidal capacity of neutrophils and macrophages measured by reactive oxygen species generation was not affected. Similarly, ex vivo rIFN-λ treatment of HSV-1–stimulated bone marrow–derived neutrophils significantly promoted IFN-stimulated genes without affecting reactive oxygen species production. Collectively, our data demonstrate that exogenous topical rIFN-λ treatment during the development and progression of SK could represent a novel therapeutic approach to control HSV-1–induced inflammation and associated vision impairment.
- Subjects :
- Cytotoxicity, Immunologic
Neutrophils
Immunology
Inflammation
Herpesvirus 1, Human
Biology
medicine.disease_cause
Antiviral Agents
Pathogenesis
Cornea
03 medical and health sciences
Mice
0302 clinical medicine
Immunopathology
medicine
Immune Tolerance
Immunology and Allergy
Animals
Humans
Corneal epithelium
chemistry.chemical_classification
Reactive oxygen species
Mucous Membrane
Macrophages
Immunity, Innate
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
Herpes simplex virus
chemistry
Keratitis, Herpetic
Cytokines
medicine.symptom
Reactive Oxygen Species
Ex vivo
030215 immunology
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 206
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....1f62f0f78cabc5e00d89047c40b47771