Interferon (IFN)-alpha/beta, interleukin (IL)-12 and IL-18 coordinately induce production of IFN-gamma during infection with herpes simplex virus type 2.
Interferons (IFNs) are important mediators of antiviral activity. In this study we have investigated how production of IFN-gamma is induced during herpes simplex virus type 2 (HSV-2) infection in murine peritoneal cells (PCs). We found that HSV-2 infection of thioglycolate-activated PCs from BALB/c mice rapidly led to expression of type 1 IFNs (IFN-alpha/beta) and interleukin (IL)-12, which was followed by production of IFN-gamma. IL-12 alone induced the most expression of IFN-gamma, which was augmented by cotreatment with IFN-alpha or IL-18, or combinations of IFN-alpha and IL-18. Moreover, neutralization of any of these cytokines in vitro strongly reduced the production of IFN-gamma, and neutralization of all three cytokines totally prevented HSV-2-induced IFN-gamma expression. Our data suggest that IFN-gamma production is induced during HSV-2 infection through the coordinated action of IFN-alpha/beta, IL-12 and IL-18.
Malmgaard
Lene
L
Department of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
Paludan
Søren R
SR
Department of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000502:physiology*; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000494:pharmacology / Q000502:physiology*; D017737:Macrophages, Peritoneal; D051379:Mice; D008807:Mice, Inbred BALB C
D007370:Interferon Type I; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma