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.
Reed
S G
SG
Seattle Biomedical Research Institute, Washington 98109.
da Silva
J S
JS
Ho
J L
JL
Koehler
J K
JK
Russo
D M
DM
Pihl
D L
DL
Coombs
R W
RW
D000818:Animals; D002478:Cells, Cultured; D056890:Eukaryota / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000469:parasitology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000469:parasitology*; D016897:Respiratory Burst / Q000187:drug effects; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure
D007371:Interferon-gamma