Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination

The Journal of Immunology : Official Journal of the American Association of Immunologists
Brett S MarroThomas E Lane

Abstract

The functional role of the ELR(+) chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G(+)CD11b(+) neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Ne...Continue Reading

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Citations

Aug 16, 2018·Viral Immunology·Dominic SkinnerThomas E Lane
Dec 19, 2019·DNA and Cell Biology·Dominic D Skinner, Thomas E Lane
Aug 2, 2017·European Journal of Anaesthesiology·Beatrice Beck-SchimmerMartin Schläpfer
Dec 24, 2018·Journal of Clinical Medicine·Yuting ChengThomas E Lane
Feb 8, 2018·Frontiers in Cellular and Infection Microbiology·Min H KangByung S Kim
Feb 9, 2021·Reviews in the Neurosciences·Dian Eurike Septyaningtrias, Rina Susilowati
Nov 10, 2020·Seminars in Cell & Developmental Biology·Leslie Kirby, Gonçalo Castelo-Branco
Dec 30, 2021·Expert Review of Clinical Immunology·Gema Olivarria, Thomas E Lane

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