Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.
Virology
; 302(2): 286-93, 2002 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-12441072
STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response. Conversely, they have elevated levels of IL-2 and thus an increased T(H)1-mediated immune response. To assess the relative impact of reduced T(H)2- and elevated T(H)1-dependent immune responses on HSV-1 infection, vaccinated and mock-vaccinated STAT6-/- mice were challenged ocularly with HSV-1. Mock-vaccinated STAT6-/- mice were as susceptible to lethal HSV-1 infection as parental BALB/c mice. Mock-vaccinated STAT6-/- mice had reduced HSV-1 titers in their eyes compared to BALB/c mice. Furthermore, mock-vaccinated STAT6-/- mice had significantly less corneal scarring than their BALB/c counterparts. Vaccination induced significantly higher serum-neutralizing antibody titers in STAT6-/- mice compared to BALB/c mice, while completely protecting both types of mice against HSV-1-induced death and corneal scarring. Vaccinated STAT6-/- mice had reduced HSV-1 titers in their eyes compared to BALB/c mice. Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1. Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice. Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated. This, in turn, leads to faster viral clearance and, consequently, lower levels of eye disease.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Interleucina-2
/
Queratitis Herpética
/
Herpesvirus Humano 1
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Virology
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos