IFN-gamma is not required in the IL-12 response to vesicular stomatitis virus infection of the olfactory bulb.
In this report, the role of IFN-gamma in host defense to exogenous IL-12 and clearance of vesicular stomatitis virus (VSV) from the central nervous system was examined. Wild-type and IFN-gamma knockout mice infected with VSV were treated with IL-12 or medium. In both groups, IL-12 treatment resulted in 1) substantially decreased VSV titers in brain homogenates and diminished immunohistochemical detection of VSV Ags in tissue sections; 2) induction of types 1, 2, and 3 nitric oxide synthase; and 3) induction of MHC molecules and rapid infiltration of both T cells and NK cells. These results suggest that IFN-gamma production, both systemically and in the olfactory bulb, contributes to but is not essential for clearance of VSV from the brain. Neutralization of TNF-alpha in IFN-gamma knockout mice mice treated with IL-12 was accompanied by the same immunohistochemical changes, implying that neither IFN-gamma nor TNF-alpha was required. In vitro studies using purified IL-12 or IFN-gamma in culture medium induced nitric oxide synthase isoforms in neurons, glia, and macrophages, and MHC II on glia and macrophages. These data suggest that IL-12 directly activates neurons to promote viral clearance in vivo.
Komatsu
T
T
Department of Biology, New York University 10003, USA.
Reiss
C S
CS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000276:immunology; D004790:Enzyme Induction / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D009830:Olfactory Bulb / Q000201:enzymology / Q000473:pathology / Q000821:virology*; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*
D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase