Host defense mechanisms against murine cytomegalovirus infection induced by poly I:C in severe combined immune deficient (SCID) mice.
The role of host defense mechanism against murine cytomegalovirus (MCMV) infection in mice with severe combined immunodeficiency (SCID) was investigated using polyinosinic:polycytidylic acid (poly I:C) as a nonspecific stimulator of the immune system. When administered ip at doses of 3.7 or 15 mg/kg 18 hr prior to infection of SCID mice with 10(3) or 10(4) plaque-forming units of MCMV, poly I:C significantly increased the animals' life span. Poly I:C enhanced, in a dose-dependent manner (0.01-1 mg/kg), the peritoneal natural killer (NK)-cell activity and macrophage activity of SCID mice. When SCID mice were pretreated with anti-asialo GM1 antibody (against NK cells) or anti-Mac1 antibody (against macrophages), poly I:C failed to stimulate the activity of NK cells and macrophages. Intraperitoneal administration of poly I:C also induced both early (2 hr) and late (18 hr) type interferon (IFN) in the peritoneal fluid and blood. The IFN-inducing activity of polyl:C was not affected by pretreatment of the mice with anti-asialo GM1 or anti-Mac1 antibody. Poly I:C also caused a significant but less pronounced increase in the life span of MCMV-infected SCID mice in which the NK cells or macrophages had been depleted by treatment with anti-asialo GM1 or anti-Mac1 antibody, respectively. These results suggest that poly I:C-induced interferon as well as activation of NK cell and macrophages contribute to the host defense mechanism against MCMV infection in SCID mice.
Ikeda
S
S
Rega Institute for Medical Research, K.U. Leuven, Belgium.
Neyts
J
J
De Clercq
E
E
D000818:Animals; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology*; D007372:Interferons / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018146:Muromegalovirus; D011070:Poly I-C / Q000494:pharmacology*
D007372:Interferons; D011070:Poly I-C