{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:39:39Z","timestamp":1790915979923,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intracerebral inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) normally results in fatal CD8+ T cell mediated meningoencephalitis. However, in CXCL10-deficient mice, the virus-induced CD8+ T cell accumulation in the neural parenchyma is impaired, and only 30\u201350% of the mice succumb to the infection. Similar results are obtained in mice deficient in the matching chemokine receptor, CXCR3. Together, these findings point to a key role for CXCL10 in regulating the severity of the LCMV-induced inflammatory process. For this reason, we now address the mechanisms regulating the expression of CXCL10 in the CNS of LCMV-infected mice. Using mice deficient in type I IFN receptor, type II IFN receptor, or type II IFN, as well as bone marrow chimeras expressing CXCL10 only in resident cells or only in bone marrow-derived cells, we analyzed the up-stream regulation as well as the cellular source of CXCL10. We found that expression of CXCL10 initially depends on signaling through the type I IFN receptor, while late expression and up-regulation requires type II IFN produced by the recruited CD8+ T cells. Throughout the infection, the producers of CXCL10 are exclusively resident cells of the CNS, and astrocytes are the dominant expressors in the neural parenchyma, not microglial cells or recruited bone marrow-derived cell types. These results are consistent with a model suggesting a bidirectional interplay between resident cells of the CNS and the recruited virus-specific T cells with astrocytes as active participants in the local antiviral host response.<\/jats:p>","DOI":"10.4049\/jimmunol.182.2.1079","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:00:37Z","timestamp":1397847637000},"page":"1079-1087","source":"Crossref","is-referenced-by-count":41,"title":["Fulminant Lymphocytic Choriomeningitis Virus-Induced Inflammation of the CNS Involves a Cytokine-Chemokine-Cytokine-Chemokine Cascade"],"prefix":"10.1093","volume":"182","author":[{"given":"Jeanette E","family":"Christensen","sequence":"first","affiliation":[{"name":"University of Copenhagen, Department of International Health, Immunology and Microbiology , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Simonsen","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Department of International Health, Immunology and Microbiology , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fenger","sequence":"additional","affiliation":[{"name":"University of Southern Denmark, Medical Biotechnology Center, Institute of Medical Biology , Odense,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Department of International Health, Immunology and Microbiology , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Moos","sequence":"additional","affiliation":[{"name":"Aalborg University, Department of Health Science and Technology , Aalborg,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P","family":"Christensen","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Department of International Health, Immunology and Microbiology , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente","family":"Finsen","sequence":"additional","affiliation":[{"name":"University of Southern Denmark, Medical Biotechnology Center, Institute of Medical Biology , Odense,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan R","family":"Thomsen","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Department of International Health, Immunology and Microbiology , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,1,15]]},"reference":[{"key":"2026012806204205700_R1","first-page":"58","article-title":"Immunity to homologous grafted skin, III: the fate of skin homografts transplanted to the brain, to subcutanous tissue, and to anterior chamber of the eye.","volume-title":"Br. J. Exp. Pathol.","year":"1948"},{"key":"2026012806204205700_R2","first-page":"485","article-title":"The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms.","volume-title":"Trends Immunol.","year":"2005"},{"key":"2026012806204205700_R3","first-page":"48","article-title":"CNS immune privilege: hiding in plain sight.","volume-title":"Immunol. Rev.","year":"2006"},{"key":"2026012806204205700_R4","first-page":"599","article-title":"The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system.","volume-title":"Neuroscience","year":"1996"},{"key":"2026012806204205700_R5","first-page":"118","article-title":"Basic principles of immunological surveillance of the normal central nervous system.","volume-title":"Glia","year":"2001"},{"key":"2026012806204205700_R6","first-page":"1033","article-title":"Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity.","volume-title":"Cell","year":"1991"},{"key":"2026012806204205700_R7","first-page":"119","article-title":"Regulation of T cell migration during viral infection: role of adhesion molecules and chemokines.","volume-title":"Immunol. Lett.","year":"2003"},{"key":"2026012806204205700_R8","first-page":"192","article-title":"Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies.","volume-title":"J. Neuroimmunol.","year":"2001"},{"key":"2026012806204205700_R9","first-page":"807","article-title":"Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients.","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2026012806204205700_R10","first-page":"6873","article-title":"CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1\u03b1 and IP-10 are expressed in demyelinating brain lesions.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2026012806204205700_R11","first-page":"59","article-title":"Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system.","volume-title":"J. Neuroimmunol.","year":"2002"},{"key":"2026012806204205700_R12","first-page":"1855","article-title":"Both CXCR3 and CXCL10\/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012806204205700_R13","first-page":"11457","article-title":"Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis.","volume-title":"J. Virol.","year":"2005"},{"key":"2026012806204205700_R14","first-page":"121","article-title":"Coronavirus infection of the central nervous system: host-virus stand-off.","volume-title":"Nat. Rev. Microbiol.","year":"2006"},{"key":"2026012806204205700_R15","first-page":"4849","article-title":"Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3.","volume-title":"J. Neurosci.","year":"2004"},{"key":"2026012806204205700_R16","first-page":"4235","article-title":"CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012806204205700_R17","first-page":"1767","article-title":"Opposing effects of CXCR3 and CCR5 deficiency on CD8+ T cell-mediated inflammation in the central nervous system of virus-infected mice.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012806204205700_R18","first-page":"675","article-title":"The effects of pretreatment with x-rays on the pathogenesis of lymphocytic choriomeningitis in mice, I: host survival, virus multiplication and leukocytosis.","volume-title":"J. Immunol.","year":"1961"},{"key":"2026012806204205700_R19","first-page":"335","article-title":"Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease.","volume-title":"Nature","year":"1972"},{"key":"2026012806204205700_R20","first-page":"8","article-title":"The acute inflammatory process in murine lymphocytic choriomeningitis is dependent on Lyt-2+ immune T cells.","volume-title":"Cell Immunol.","year":"1987"},{"key":"2026012806204205700_R21","first-page":"55","article-title":"Dissection of an inflammatory process induced by CD8+ T cells.","volume-title":"Immunol. Today","year":"1990"},{"key":"2026012806204205700_R22","first-page":"373","article-title":"The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice.","volume-title":"Scand. J. Immunol.","year":"1994"},{"key":"2026012806204205700_R23","first-page":"559","article-title":"Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen.","volume-title":"Nature","year":"1989"},{"key":"2026012806204205700_R24","first-page":"520","article-title":"Immunological unresponsiveness of nude mice to LCM virus infection.","volume-title":"Acta Pathol. Microbiol. Scand.","year":"1976"},{"key":"2026012806204205700_R25","first-page":"657","article-title":"Estimating the precursor frequency of naive antigen-specific CD8 T cells.","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026012806204205700_R26","first-page":"e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR.","volume-title":"Nucleic Acids Res.","year":"2001"},{"key":"2026012806204205700_R27","first-page":"175","article-title":"A specific and sensitive method for visualization of tumor necrosis factor in the murine central nervous system.","volume-title":"Brain Res.","year":"2001"},{"key":"2026012806204205700_R28","first-page":"256","article-title":"pppA2\u2032p5\u2032A2\u2032p5\u2032A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1978"},{"key":"2026012806204205700_R29","first-page":"6355","article-title":"Interferon action and apoptosis are defective in mice devoid of 2\u2032,5\u2032-oligoadenylate-dependent RNase L.","volume-title":"EMBO J.","year":"1997"},{"key":"2026012806204205700_R30","first-page":"1797","article-title":"CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection.","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026012806204205700_R31","first-page":"202","article-title":"Role of interferon-\u03b3 in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-\u03b3 knock-out mice.","volume-title":"J. Neuroimmunol.","year":"1998"},{"key":"2026012806204205700_R32","first-page":"12378","article-title":"Role of macrophage inflammatory protein-1\u03b1 in T-cell-mediated immunity to viral infection.","volume-title":"J. Virol.","year":"2003"},{"key":"2026012806204205700_R33","first-page":"6838","article-title":"Among CXCR3 chemokines, IFN-\u03b3-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-\u03b3 (CXCL9) imprints a pattern for the subsequent development of autoimmune disease.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012806204205700_R34","first-page":"18651","article-title":"Tissue-specific positive feedback requirements for production of type I interferon following virus infection.","volume-title":"J. Biol. Chem.","year":"2005"},{"key":"2026012806204205700_R35","first-page":"65","article-title":"Chemokines and the inflammatory response to viral infection in the central nervous system with a focus on lymphocytic choriomeningitis virus.","volume-title":"J. Neurovirol.","year":"1999"},{"key":"2026012806204205700_R36","first-page":"47","article-title":"The timing of the immune response in relation to virus growth determines the outcome of the LCM infection.","volume-title":"Acta Pathol. Microbiol. Scand.","year":"1979"},{"key":"2026012806204205700_R37","first-page":"131","article-title":"Innate immune recognition of viral infection.","volume-title":"Nat. Immunol.","year":"2006"},{"key":"2026012806204205700_R38","first-page":"675","article-title":"Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.","volume-title":"Immunity","year":"2008"},{"key":"2026012806204205700_R39","first-page":"4776","article-title":"IFN-\u03b2 gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012806204205700_R40","first-page":"7514","article-title":"Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during viral infection.","volume-title":"J. Virol.","year":"2005"},{"key":"2026012806204205700_R41","first-page":"925","article-title":"Viruses selectively upregulate Toll-like receptors in the central nervous system.","volume-title":"Biochem. Biophys. Res. Commun.","year":"2005"},{"key":"2026012806204205700_R42","first-page":"7832","article-title":"Chemokine gene expression in the brains of mice with lymphocytic choriomeningitis.","volume-title":"J. Virol.","year":"1997"},{"key":"2026012806204205700_R43","first-page":"89","article-title":"T-cell-mediated immunopathology in viral infections.","volume-title":"Transplant. Rev.","year":"1974"},{"key":"2026012806204205700_R44","first-page":"31","article-title":"Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice.","volume-title":"Nature","year":"1994"},{"key":"2026012806204205700_R45","first-page":"1222","article-title":"Perforin-deficient CD8+ T cells mediate fatal lymphocytic choriomeningitis despite impaired cytokine production.","volume-title":"J. Virol.","year":"2006"},{"key":"2026012806204205700_R46","first-page":"7835","article-title":"Neurons produce type I interferon during viral encephalitis.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2006"},{"key":"2026012806204205700_R47","first-page":"24","article-title":"Pro-inflammatory functions of astrocytes correlate with viral clearance and strain-dependent protection from TMEV-induced demyelinating disease.","volume-title":"Virology","year":"2008"},{"key":"2026012806204205700_R48","first-page":"70","article-title":"Lymphocytic Choriomeningitis Virus (LCMV) infection of CNS glial cells results in TLR2-MyD88\/Mal-dependent inflammatory responses.","volume-title":"J. Neuroimmunol.","year":"2008"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/2\/1079\/62679693\/8384.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/2\/1079\/62679693\/8384.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:20:50Z","timestamp":1769599250000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/2\/1079\/8004350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":48,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,1,15]]},"published-print":{"date-parts":[[2009,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.182.2.1079","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,1]]},"published":{"date-parts":[[2009,1]]}}}