Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent

Patric Lundberg, Harry Openshaw, Mingwu Wang, Hui Jung Yang, Edouard Cantin

Research output: Contribution to journalArticle

20 Citations (Scopus)

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-γ (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.

Original languageEnglish (US)
Pages (from-to)4162-4170
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Encephalitis
Simplexvirus
Skin Diseases
Virus Diseases
Corneal Diseases
129 Strain Mouse
Survival
Cornea
Monoclonal Antibodies
Chemokine CXCL10
Monokines
Inflammation
Eye Infections
Nerve Tissue
Keratitis
Central Nervous System Diseases
Neutralizing Antibodies
Chemokines
Interferons
Nervous System

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent. / Lundberg, Patric; Openshaw, Harry; Wang, Mingwu; Yang, Hui Jung; Cantin, Edouard.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 9, 09.2007, p. 4162-4170.

Research output: Contribution to journalArticle

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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-γ (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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T1 - Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent

AU - Lundberg, Patric

AU - Openshaw, Harry

AU - Wang, Mingwu

AU - Yang, Hui Jung

AU - Cantin, Edouard

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N2 - 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-γ (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.

AB - 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-γ (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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