Macrophage dependence of polyriboinosinic acid-polyribocytidylic acid-induced resistance to herpes simplex virus infection in mice.
The relative contributions of macrophages and lymphocytes to the induction of resistance to primary herpes simplex virus type 1 (HSV-1) infection by polyriboinosinic-polyribocytidylic acid complex [poly (I:C)] were investigated in C58 mice. The induction of resistance was found to be strongly dependent on macrophages compared to lymphocytes. Macrophage-deficient (silica-treated) mice produced less interferon and were not as responsive to prophylactic treatment of HSV-1 infections with poly (I:C) as were either normal, lymphocyte-deficient (cyclophosphamide-treated), or T-lymphocyte-deficient (anti-thymocyte serum-treated, adult-thymectomized) mice. Silica and cyclophosphamide treatments reduced the therapeutic activity of poly (I:C), whereas T-cell depletion did not have a significant effect. Similarly, the protection of mice with exogenous interferon was markedly reduced in silica-treated mice and moderately reduced in cyclophosphamide-treated mice, but unaffected in T-cell-deficient mice. Furthermore, suppression of HSV-1 plaque formation was obtained by cocultivation of infected mouse fibroblast monolayers with peritoneal (macrophage-rich) cells, but not with splenic (lymphocyte-rich) cells, from poly (I:C)-treated mice. Peritoneal cells did not protect heterologous (human) fibroblasts, suggesting that the protection of mouse embryo fibroblasts is mediated by interferon. Collectively, the data indicate that macrophages are required for the production of poly (I:C)-induced interferon and that macrophages and perhaps B-lymphocytes are important for mediating the protection against HSV-1 infection after interferon has been produced.
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D007372:Interferons / Q000096:biosynthesis*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D011070:Poly I-C / Q000627:therapeutic use*; D018139:Simplexvirus / Q000254:growth & development; D013601:T-Lymphocytes / Q000502:physiology
D007372:Interferons; D011070:Poly I-C