Effect of IFN-gamma on the proliferation of Toxoplasma gondii in monocytes and monocyte-derived macrophages from AIDS patients.
This study was undertaken to determine whether the activity of monocytes and monocyte-derived macrophages (MDM) from acquired immune deficiency syndrome (AIDS) patients against Toxoplasma gondii is altered and whether this activity can be modulated by recombinant interferon-gamma (rIFN-gamma). Untreated and rIFN-gamma-treated monocytes or MDM from AIDS patients and from healthy controls were infected with T. gondii and the proliferation of these protozoa was determined. The H2O2 release by monocytes from AIDS patients and healthy controls was measured upon stimulation with phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). Monocytes from AIDS patients exhibited significantly lower toxoplasmastic activity compared to monocytes from healthy controls. The H2O2 release by monocytes from AIDS patients was also diminished. Incubation of monocytes from AIDS patients with rIFN-gamma for 2 days, but not 1 day, restored their toxoplasmastatic activity. The rate of proliferation of T. gondii was higher in MDM from AIDS patients than in MDM from healthy controls. Treatment of MDM from AIDS patients with rIFN-gamma for 1, 2 or 3 days resulted in partial inhibition of the proliferation of T. gondii. Collectively, these results demonstrate that the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients can be enhanced by in vitro treatment with rIFN-gamma, which supports the clinical use of rIFN-gamma for the treatment of opportunistic infections in these patients.
Delemarre
F G
FG
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Stevenhagen
A
A
Kroon
F P
FP
van Eer
M Y
MY
Meenhorst
P L
PL
van Furth
R
R
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins; D014122:Toxoplasma / Q000254:growth & development; D014123:Toxoplasmosis / Q000276:immunology*; D015215:Zidovudine / Q000494:pharmacology
D011994:Recombinant Proteins; D015215:Zidovudine; D007371:Interferon-gamma; D006861:Hydrogen Peroxide