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Human immunodeficiency virus causes mononuclear phagocyte dysfunction
G C Baldwin1, J Fleischmann, Y Chung
1Division of Hematology-Oncology, UCLA School of Medicine 90024.
Abstract:
There is compelling clinical evidence for dysfunction of the mononuclear phagocyte system in patients with AIDS, which is believed due in part to loss of T-cell cooperativity. The direct consequences of human immunodeficiency virus infection on macrophage function are unknown. To address this question we infected normal human macrophages in vitro with a monocytotropic strain of human immunodeficiency virus and performed assays to quantify their extra- and intracellular killing ability. Human immunodeficiency virus-infected macrophages were significantly less effective than control cells in mediating antibody-dependent cell-mediated cytotoxicity against leukemic cell targets and intracellular killing of Candida pseudotropicalis. The functional defects were profound, related temporarily to active virus production by the macrophages, and could not be overcome by granulocyte-macrophage colony-stimulating factor. Treatment of macrophages with 3'-azido-3'-deoxythymidine (AZT) 6 days after infection caused a marked decrease in virus production and prevented development of the intracellular killing functional defect. The results suggest that early antiviral therapy may be useful in preventing or mitigating some virus-induced mononuclear phagocyte dysfunction.
Insights
Human immunodeficiency virus (HIV) infection impairs macrophage function, reducing their ability to kill pathogens and tumor cells. Early treatment with azidothymidine (AZT) can restore macrophage function by decreasing viral load.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Mononuclear phagocyte system dysfunction is observed in acquired immunodeficiency syndrome (AIDS) patients, potentially due to T-cell loss.
- The direct impact of human immunodeficiency virus (HIV) on macrophage function remains unclear.
Purpose of the Study:
- To investigate the direct effects of HIV infection on human macrophage functions, specifically their extra- and intracellular killing capabilities.
Main Methods:
- Normal human macrophages were infected in vitro with a monocytotropic strain of HIV.
- Assays were performed to quantify the antibody-dependent cell-mediated cytotoxicity (ADCC) and intracellular killing of Candida pseudotropicalis.
Main Results:
- HIV-infected macrophages exhibited significantly reduced efficacy in ADCC against leukemic targets and intracellular killing of C. pseudotropicalis compared to control cells.
- These functional defects correlated with active virus production and were not improved by granulocyte-macrophage colony-stimulating factor.
- Treatment with 3'-azido-3'-deoxythymidine (AZT) post-infection decreased viral production and prevented the development of impaired intracellular killing.
Conclusions:
- HIV directly impairs critical macrophage functions, impacting host defense mechanisms.
- Early antiviral therapy, such as AZT, may preserve macrophage function by controlling viral replication.