Unaltered neurological disease and mortality in CXCR3-deficient mice infected intracranially with lymphocytic choriomeningitis virus-Armstrong.
Intracranial infection of mice with lymphocytic choriomeningitis virus (LCMV) results in a lethal neurological disease termed lymphocytic choriomeningitis (LCM) that is mediated by antiviral CD8(+) T cells. Previous studies have implicated the chemokine receptor CXCR3 and its ligand CXCL10 in CD8(+) T cell trafficking in the brain and in the lethal disease following intracranial infection of mice with the LCMV-Traub strain. Here we investigated the role of CXCR3 in LCM following intracranial infection of mice with the LCMV-Armstrong strain. Significant induction of both CXCL9 and CXCL10 RNA and protein was seen in the central nervous system (CNS) in LCM. Cellular localization of the CXCL9 and CXCL10 RNA transcripts was identified predominantly in infiltrating mononuclear cells, as well as in subpial and paraventricular microglia (CXCL9) and astrocytes (CXCL10). Despite a primary role of interferon (IFN)-gamma in inducing the expression of the CXCL9 gene, and to a lesser extent the CXCL10 gene in LCM, the absence of the IFN-gamma receptor did not influence the disease outcome. This finding suggested that these chemokines may not play a major role in the pathogenesis of LCM. To evaluate this possibility further the development of LCM was examined in mice that were deficient for CXCR3. Surprisingly, in the absence of CXCR3 there was no alteration in mortality, cytokine expression, or T cell infiltration in the CNS, demonstrating that in contrast to LCMV-Traub, CXCR3 is not involved in the pathogenesis of LCMV-Armstrong-induced neurological disease in mice. Our findings indicate that despite similar immunopathogenetic mechanisms involving antiviral CD8(+) T cells, whether or not CXCR3 signaling has a role in LCM is dependent upon the infecting strain of LCMV.
Hofer
Markus J
MJ
School of Molecular and Microbial Biosciences and the Bosch Institute, The University of Sydney, New South Wales, Australia.
Carter
Sally L
SL
Müller
Marcus
M
Campbell
Iain L
IL
D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000821:virology; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000401:mortality* / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009026:Mortality; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology*
D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D007371:Interferon-gamma