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Patric Lundberg, Harry Openshaw, Mingwu Wang, Hui-Jung Yang, Edouard Cantin; 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. 2007;48(9):4162-4170. doi: https://doi.org/10.1167/iovs.07-0261.
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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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