Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system.
Induction of a Th1 immune response against viral infection of the CNS is important in contributing to viral clearance. The present studies demonstrate a role for the T cell chemoattractant chemokine Mig (monokine induced by IFN-gamma) in contributing to a Th1 response against mouse hepatitis virus infection of the CNS. Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection. To determine functional significance, mouse hepatitis virus-infected mice were treated with anti-Mig antisera, and the severity of disease was evaluated. Such treatment resulted in a marked increase in mortality that correlated with a >3 log increase in viral burden within the brains as compared with control mice treated with normal rabbit serum. Anti-Mig-treated mice displayed a significant decrease (p < 0.005) in CD4(+) and CD8(+) T cell recruitment into the CNS as compared with normal rabbit serum-treated mice. In addition, anti-Mig treatment resulted in a significant decrease (p < 0.05) in levels of IFN-gamma and IFN-beta that coincided with increased (p < 0.02) expression of the anti-inflammatory Th2 cytokine IL-10 within the CNS. Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS.
Liu
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Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Armstrong
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Hamilton
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Lane
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D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D018792:Encephalitis, Viral / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D016207:Cytokines; D007106:Immune Sera; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma