Effect of mercuric chloride on macrophage-mediated resistance mechanisms against infection with herpes simplex virus type 2.
Macrophages play an important role in the early, nonspecific resistance to infection with herpes simplex virus. Mercuric chloride (HgCl2) accumulates in macrophages and has in certain concentrations a marked influence on the functional capacity of these cells. Therefore the influence of HgCl2 on resistance to generalized infection with herpes simplex virus type 2 (HSV-2) in mice and its effect on the HSV-2-induced activation of macrophages in vitro was examined. Mice injected intraperitoneally with HgCl2 24 h before infection with HSV-2 had more than 100 times higher virus titres in the liver 4 days after infection than mice not receiving any mercury. HgCl2 exerted a toxic effect on macrophages in vitro, which was especially pronounced during their adherence. Macrophages infected with HSV-2 were activated for an enhanced respiratory burst. This activation was abolished by treatment of the cells for 24 h with relatively low concentrations of HgCl2, resulting in macrophages with a potential to react with a respiratory burst comparable to that of uninfected cells. The HSV-2-induced activation of macrophages is mediated through the production and synergistic interaction of interferon-alpha/beta and tumour necrosis factor-alpha in an autocrine manner. The ability of these cytokines to activate macrophages and to interact synergistically was not affected by mercury. However the production by macrophages of both cytokines during the HSV-2 infection, but especially interferon-alpha/beta, which is essential for the activation, was reduced at low concentrations of HgCl2. Collectively these data indicate that mercury, by interfering with the early macrophage-production of cytokines, disables the early control of virus replication, leading to an enhanced infection.
Ellermann-Eriksen
S
S
Institute of Medical Microbilogy, University of Aarhus, Denmark.
Christensen
M M
MM
Mogensen
S C
SC
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D008627:Mercuric Chloride; D007372:Interferons