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Macrophage-colony stimulating factor (M-CSF) stimulation induces cell death in HIV-infected human monocytes
A Bergamini1, M Capozzi, M Piacentini
1Department of Public Health and Cell Biology, University of Rome Tor Vergata, Italy.
Abstract:
We show here that HIV-infected monocyte-macrophages stimulated by macrophage-colony stimulating factor (M-CSF) undergo massive syncytia formation and die. The M-CSF-stimulated HIV-infected monocyte-macrophages (M/M) destroy themselves by blebbing out particles (resembling apoptotic bodies) which may contain condensed and marginated chromatin. The death of monocyte-macrophages is also characterized by the expression of "Tissue" Transglutaminase (tTG) which is one of the genes specifically expressed and activated in apoptising cells. Noteworthy, when the syncytia formation and consequently death is prevented, infected monocyte-macrophages remain viable and produce large amounts of virus for an extended period. The concentrations of M-CSF (1000 U/ml) used in this work are similar to those that stimulate macrophages in vivo. This suggests that HIV killing of M/M in the presence of M-CSF could lead, in vivo, to a greater than expected loss of immune cells and may contribute to explain the complex derangement of the immune function observed in HIV-infected patients.
Insights
Macrophage-colony stimulating factor (M-CSF) triggers HIV-infected macrophages to form syncytia and die. Preventing this cell death increases HIV production, impacting immune function in patients.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) infects monocyte-macrophages, crucial immune cells.
- Macrophage-colony stimulating factor (M-CSF) is vital for macrophage survival and function.
- The interplay between HIV infection, M-CSF, and macrophage fate is not fully understood.
Purpose of the Study:
- To investigate the effect of M-CSF on HIV-infected monocyte-macrophages.
- To elucidate the mechanisms of cell death in M-CSF-stimulated, HIV-infected macrophages.
- To determine the impact of M-CSF-induced cell death on viral production.
Main Methods:
- Primary human monocyte-macrophages were infected with HIV.
- Cells were stimulated with M-CSF (1000 U/ml).
- Syncytia formation, cell viability, viral production, and expression of tissue transglutaminase (tTG) were assessed.
Main Results:
- M-CSF stimulation induced massive syncytia formation and death in HIV-infected monocyte-macrophages.
- Cell death involved blebbing of particles with condensed chromatin and expression of tTG.
- Inhibition of syncytia formation allowed infected macrophages to survive and produce high levels of HIV.
- M-CSF concentrations used mimic physiological levels.
Conclusions:
- M-CSF-induced syncytia formation and death represent a significant mechanism of immune cell loss in HIV infection.
- This process, driven by M-CSF, contributes to the observed immune dysfunction in HIV-infected individuals.
- Targeting M-CSF-mediated cell death could be a therapeutic strategy to preserve immune cells and control viral load.