Endogenous Interferon- , Macrophage Activation, and Murine Host Defense against Acute Infection with Trypanosoma cruzi

Abstract

Parenteral interferon-γ (IFN-γ) activates murine macrophages to inhibit Trypanosoma cruzi multiplication and diminishes parasitemia and mortality in acute infection. To investigate the role of endogenous IFN-γ in acute infection, monoclonal antibody to IFN-γ was injected intraperitoneally into mice. The 6250 neutralizing units given 24 and 96 h after infection reproducibly increased mortality (P < .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-γ. Peritoneal macrophages from mice 4 days after infection and a single dose of 6250 units of anti-IFN-γ had significantly reduced ability to inhibit T. cruzi multiplication. Multiple doses of anti-IFN-γ delayed but did not prevent macrophage activation. These results indicate the critical role of endogenous IFN-γ for macrophage activation and host defense against acute T. cruzi infection in mice.