Sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of T cell-dependent production of interferon-gamma.
The interplay between viral infection and lipopolysaccharide (LPS) was studied. Infection with a noncytopathogenic virus, lymphocytic choriomeningitis virus (LCMV), was found to sensitize mice to low doses of LPS. In vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-alpha (TNF-alpha), and in vitro, LPS-stimulated splenic adherent cells produced increased amounts of TNF-alpha. Hyperproduction of TNF-alpha was temporally correlated with virus-induced production of interferon-gamma (IFN-gamma); only marginally increased IFN-gamma and TNF-alpha production was observed in LCMV-infected, T cell-deficient mice and in mice infected with vesicular stomatitis virus, a virus that induces much less T cell activation than does LCMV. Finally, LCMV infection was much less efficient in priming IFN-gamma knockout mice for hyperproduction of TNF-alpha. These findings indicate that clinically silent viral infections may induce hypersensitivity to LPS through T cell activation and subsequent production of IFN-gamma; this sensitizes monocytes/macrophages for hyperproduction of TNF-alpha.
Nansen
A
A
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Christensen
J P
JP
Marker
O
O
Thomsen
A R
AR
D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma