HIV-1-infected peripheral blood mononuclear cells enhance neutrophil survival and HLA-DR expression via increased production of GM-CSF: implications for HIV-1 infection

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 56; no. 1; p. 16
• Main Authors: Fu, Jun, Sha, Beverly E, Thomas, Larry L
• Format: Journal Article
• Language: English
• Published: United States 01.01.2011
• Subjects: Adult; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Flow Cytometry; Gene Expression Regulation - immunology; Gene Expression Regulation - physiology; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; HIV Infections - immunology; HIV Infections - physiopathology; HIV Infections - virology; HIV-1 - physiology; HLA-DR Antigens - biosynthesis; Humans; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - physiology; Leukocytes, Mononuclear - virology; Neutrophil Activation - drug effects; Neutrophil Activation - physiology; Neutrophils - drug effects; Neutrophils - physiology; Neutrophils - virology; Phytohemagglutinins - pharmacology
• ISSN: 1944-7884
• DOI: 10.1097/QAI.0b013e3181fa1fa5

HIV-1 bound to intact neutrophils efficiently infects activated peripheral blood mononuclear cells (PBMC). Here, we evaluated the effect of the local milieu created by activated PBMC before and after HIV-1 infection on neutrophil survival and HLA-DR expression, with emphasis placed on a role for GM-CSF. PBMC of healthy adult individuals were activated by phytohemagglutinin (PHA) or anti-CD3/anti-CD28 and were subsequently cultured without (HIV-1⁻) or with HIV-1 (HIV-1+). The effects of the culture supernatants or recombinant GM-CSF on survival and HLA-DR expression by neutrophils of healthy adult individuals and of HIV-1-infected individuals were evaluated using flow cytometry. Conditioned medium from PHA-activated PBMC (HIV-1⁻ and HIV-1+) increased neutrophil survival and induced HLA-DR expression by neutrophils of healthy individuals in a GM-CSF dependent fashion. HIV-1 infection variably, but consistently, increased GM-CSF production by PHA-activated PBMC but not GM-CSF production by anti-CD3/anti-CD28-activated PBMC. The latter was correlated with a loss of CD3+GMCSF+ cells after infection. Neutrophils of elite controllers exhibited a diminished HLADR response to GM-CSF in culture, whereas neutrophils of HIV-1+ subjects having a low viral load on anti-retroviral therapy or subjects with a high viral load exhibited a range of HLA-DR responses. GM-CSF production within the mucosa or draining lymph nodes may promote HIV-1 infection by facilitating sustained contact between viable neutrophils with bound HIV-1 and CD4 lymphocytes. The minimal effect of GM-CSF on HLA-DR expression by neutrophils of elite controllers provides indirect support for this conclusion.