Endogenous interferon-gamma, macrophage activation, and murine host defense against acute infection with Trypanosoma cruzi.
Parenteral interferon-gamma (IFN-gamma) activates murine macrophages to inhibit Trypanosoma cruzi multiplication and diminishes parasitemia and mortality in acute infection. To investigate the role of endogenous IFN-gamma in acute infection, monoclonal antibody to IFN-gamma was injected intraperitoneally into mice. The 6250 neutralizing units given 24 and 96 h after infection reproducibly increased mortality (P less than .05). Histology sections showed markedly more nests of T. cruzi in treated mice. BALB/c, Swiss Webster, C57Bl/6, and C3H/HEN mice were susceptible to the effects of anti-IFN-gamma. Peritoneal macrophages from mice 4 days after infection and a single dose of 6250 units of anti-IFN-gamma had significantly reduced ability to inhibit T. cruzi multiplication. Multiple doses of anti-IFN-gamma delayed but did not prevent macrophage activation. These results indicate the critical role of endogenous IFN-gamma for macrophage activation and host defense against acute T. cruzi infection in mice.
McCabe
R E
RE
Medical Service, Martinez VA Medical Center, California 94553.
Meagher
S G
SG
Mullins
B T
BT
D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D007371:Interferon-gamma / Q000276:immunology*; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D007371:Interferon-gamma