IFN-gamma is not required in the IL-12 response to vesicular stomatitis virus infection of the olfactory bulb.

Abstract

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.

• Authors: T Komatsu, C S Reiss
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 159 Issue 7 Pg. 3444-52 (Oct 01 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9317143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Interferon-gamma
• Nitric Oxide Synthase

Topics

• Animals
• Antibodies (pharmacology)
• Astrocytes (drug effects, pathology)
• Brain Chemistry (drug effects)
• Cell Division (drug effects)
• Cell Movement (immunology)
• Enzyme Induction (genetics)
• Gene Expression Regulation (drug effects)
• Histocompatibility Antigens Class I (biosynthesis, drug effects)
• Histocompatibility Antigens Class II (biosynthesis, drug effects)
• Interferon-gamma (blood, genetics, physiology)
• Interleukin-12 (biosynthesis, pharmacology)
• Killer Cells, Natural (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (drug effects, pathology)
• Nitric Oxide Synthase (biosynthesis, genetics)
• Olfactory Bulb (enzymology, pathology, virology)
• Rhabdoviridae Infections (immunology, pathology)
• T-Lymphocytes (pathology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (immunology, metabolism)
• Vesicular stomatitis Indiana virus (drug effects, growth & development, immunology)