Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent.
Invest Ophthalmol Vis Sci
; 48(9): 4162-70, 2007 Sep.
Article
en En
| MEDLINE
| ID: mdl-17724202
ABSTRACT
PURPOSE:
The host inflammatory response to ocular infection with herpes simplex virus (HSV) can be either protective, with disease-free survival, or it can promote diseases such as HSV corneal disease (or herpes stromal keratitis [HSK] in humans) and encephalitis (HSE), depending on mouse strain. The role of CXCR3 chemokine signaling in HSV-induced central nervous system (CNS) inflammation and corneal disease was evaluated, and responses in genetically susceptible and resistant strains of mice were contrasted.METHODS:
Resistant C57BL/6J (B6) and susceptible 129S6 (129) mice were given monoclonal antibodies (mAbs) to neutralize the CXCR3 ligands monokine induced by interferon-gamma (MIG, CXCL9) and interferon inducible protein-10 (IP-10, CXCL10) during HSV infection. In addition, the development of HSV disease was monitored in CXCR3-null mutant mice derived from resistant (B6) and susceptible (BALB/c) strains. Inflammatory cells infiltrating the cornea and brain stem were isolated and stained for flow cytometric analysis.RESULTS:
MIG and IP-10 were induced in nervous system tissue after HSV inoculation by the corneal route. HSV-infected 129 mice treated with MIG- or IP-10-neutralizing mAbs showed significantly enhanced survival compared with mice treated with control isotype antibody, whereas survival of the B6 mice was unaltered. Similarly, greater survival was observed for BALB.CXCR3(-/-) mice compared with control BALB/c mice. Reduced CNS inflammation was documented that extended to the cornea, such that HSV corneal disease severity was reduced in susceptible BALB.CXCR3(-/-). In contrast, although survival of B6 and B6.CXCR3(-/-) mice was indistinguishable, B6.CXCR3(-/-) mice developed more severe corneal and periocular skin disease.CONCLUSIONS:
The effects of CXCR3 signaling in HSV infection are strongly dependent on mouse strain.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Queratitis Herpética
/
Enfermedades Cutáneas Virales
/
Receptores de Quimiocina
/
Encefalitis por Herpes Simple
Límite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos