Herpes simplex virus type 2 primes mouse macrophages for an early and genetically determined respiratory burst mediated by interferon-alpha/beta.
The influence of infection by herpes simplex virus type 2 (HSV-2) on the respiratory burst capacity of mouse macrophages was studied by luminol-dependent chemiluminescence with phorbol myristate acetate (PMA) as trigger. Peritoneal cells from virus-infected mice were strongly primed for a respiratory burst during the acute phase of the infection. By 12 h after infection the response had increased 40-fold over control values. Most of the response was elicited by mononuclear phagocytes. When resting peritoneal macrophages were infected with HSV-2 in vitro a maximal priming effect was seen with 2 x 10(6) p.f.u./ml of virus after 8 h, but a significant response was obtained after 4 h of infection; after 12 h incubation with virus the response declined to reach background levels at 24 h. Peritoneal cells from C57BL/6 mice which are relatively resistant to HSV-2 showed a higher respiratory burst capacity after infection than cells from more susceptible BALB/c mice. Incubation of macrophages with crude niurine interferon (IFN)-alpha/beta produced by macrophages or purified murine IFN-alpha, in concentrations comparable to those obtained early (2 to 5 h) after infection of macrophage cultures with HSV-2 also augmented the respiratory burst. Addition of an IFN-alpha/beta-specific antiserum to HSV-2-infected cultures almost completely removed the response. We therefore conclude that HSV-2 induces an early and genetically determined activation of macrophages, mediated in an autocrine manner by IFN-alpha/beta secreted by the macrophages early during infection.
Mogensen
S C
SC
Institute of Medical Microbiology, University of Aarhus, Denmark.
Ellermann-Eriksen
S
S
Sommerlund
M
M
D000818:Animals; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D008163:Luminescent Measurements; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000187:drug effects; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D007370:Interferon Type I; D013755:Tetradecanoylphorbol Acetate