Cytokine activation of human macrophages infected with HIV-1 to inhibit intracellular protozoa.

Peripheral blood mononuclear cells (PBMCs) from HIV-seronegative donors were infected in vitro with HIV-1. Infection was monitored by cytopathology, supernatant p24 antigen, and by immunocytochemical staining. After 14 days in culture, approximately 70-90% of the cells became infected with HIV, as indicated by cell fusion and immunostaining for virus. At this time, recombinant HuIFN-gamma was added to the cultures, followed by infection 24 h later with the intracellular protozoan parasites Toxoplasma gondii, Trypanosoma cruzi, or Leishmania chagasi. Percentages of intracellular parasites were determined at various points thereafter. Using a system capable of detecting both virus and parasite infection, we determined that (a) cells infected with HIV were capable of ingesting and/or being infected by each of these parasitic protozoa, (b) HIV-infected macrophages could be activated to inhibit the replication of all three parasites following treatment with IFN-gamma, and (c) cultures of HIV-infected macrophages could respond to IFN-gamma with increased oxidative burst activity. The degree of parasite infection or inhibition observed in infected cells was not significantly different from that observed in non-HIV-infected cells. From these observations, we concluded that HIV-1 infection does not render macrophages unresponsive to IFN-gamma activation for microbicidal activity.