Loss of TRPM8 Exacerbate Herpes Simplex Keratitis Infection in Mice by Promoting the Infiltration of CD11b+ Ly6G+ Cells and Increasing the Viral Load in the Cornea.
Invest Ophthalmol Vis Sci
; 64(15): 24, 2023 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-38117245
ABSTRACT
Purpose:
To reveal the role of transient receptor potential cation subfamily M member 8 (TRPM8) channels in herpes simplex keratitis (HSK).Methods:
HSK models were established using TRPM8 knockout (TRPM8-/-) mice and their wild-type (WT) littermates. The infected corneas were graded and harvested to evaluate the mRNA levels of inflammatory factors through quantitative real-time polymerase chain reaction (RT-PCR), as well as the infiltration of inflammatory cells through immunofluorescence staining and flow cytometry. Viral titers were determined by plaque assay and absolute quantitative method. RNA-sequencing was conducted to elucidate the transcriptome of corneal epithelium in response to TRPM8 knockout after infection. The anti-inflammatory effect of TRPM8 agonist menthol was documented via subconjunctival administration.Results:
Compared to their wild-type counterparts, TRPM8-deficient mice exhibited exacerbated infection symptoms and thicker corneas in HSK models. Infection in TRPM8-deficient mice resulted in significant lymphocyte infiltration, primarily consisting of Ly6G+ CD11b+ cells. Additionally, TRPM8-deficient mice displayed increased levels of corneal viral titers after infection, along with decreased expression of interferon-stimulated genes (ISGs). Subconjunctival administration of menthol effectively alleviated infection-induced symptoms and Ly6G+ CD11b+ cell infiltration in herpes simplex virus type 1 (HSV-1)-treated mice.Conclusions:
TRPM8 promoted host resistance to HSV-1 infection by suppressing the accumulation of Ly6G+ CD11b+ cells and virus replication. These findings suggest that targeting TRPM8 could be valuable for therapeutic interventions against HSV-1 infections.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Queratitis Herpética
/
Canales Catiónicos TRPM
/
Herpes Simple
Límite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
China