Both Cxcr3 and Cxcl10/Ifn-Inducible Protein 10 Are Required for Resistance to Primary Infection by Dengue Virus
Resource
JOURNAL OF IMMUNOLOGY v.177 n.3 pp.1855-1863
Journal
JOURNAL OF IMMUNOLOGY
Journal Volume
v.177
Journal Issue
n.3
Pages
1855-1863
Date Issued
2006
Date
2006
Author(s)
SUNG, JUI-MIN
WU-HSIEH, BETTY
Abstract
We examined the extent to which CXCR3 mediates resistance to dengue infection. Following intracerebral infection with dengue virus, CXCR3- deficient (CXCR3(-/-)) mice showed significantly higher mortality rates than wild-type (WT) mice; moreover, surviving CXCR3(-/-) mice, but not WT mice, often developed severe hind-limb paralysis. The brains of CXCR3-/- mice showed higher viral loads than those of WT mice, and quantitative analysis using real-time PCR, flow cytometry, and immunohistochemistry revealed fewer T cells, CD8(+) T cells in particular, in the brains of CXCR3(-/)- mice. This suggests that recruitment of effector T cells to sites of dengue infection was diminished in CXCR3-/- mice, which impaired elimination of the virus from the brain and thus increased the likelihood of paralysis and/or death. These results indicate that CXCR3 plays a protective rather than an immunopathological role in dengue virus infection. In studies to identify critical CXCR3 ligands, CXCL10/IFN- inducible protein 10-deficient (CXCL10/IP-10(-/-)) mice infected with dengue virus showed a higher mortality rate than that of the CXCR3(-/-) mice. Although CXCL10/IP-10, CXCL9/monokine induced by IFN-gamma, and CXCL 11/IFN- inducible T cell a chemoattractant share a single receptor and all three of these chemokines are induced by dengue virus infection, the latter two could not compensate for, the absence of CXCL10/IP-10 in this in vivo model. Our results suggest that both CXCR3 and CXCLIO/IP-10 contribute to resistance against primary dengue virus infection and that chemokines that are indistinguishable in in vitro assays differ in their activities in vivo.
Subjects
CENTRAL-NERVOUS-SYSTEM
CD8(+) T-CELLS
GAMMA-INDUCIBLE PROTEIN-10
CHEMOKINE EXPRESSION
IN-VIVO
HOST-DEFENSE
SDGs