Regulation of human immunodeficiency virus type 1 infection, β-chemokine production, and CCR5 expression in CD40L-stimulated macrophages

Immune control of viral entry

R. L. Cotter, Jialin C Zheng, M. Che, Douglas F Niemann, Y. Liu, J. He, E. Thomas, Howard Eliot Gendelman

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host immune response to human immunodeficiency virus type I (HIV.1) infection. Regulation of such immune responses can be mediated, in part, through the interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear cells during advanced HIV-1 disease has previously been reported. Based on this observation, we studied the influence of CD40L-CD40 interactions on MP effector function and viral regulation in vitro. We monitored productive viral infection, cytokine and β-chemokine production, and β-chemokine receptor expression in monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning 1 day after infection and continuing at 3-day intervals, treatment with CD40L inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A concomitant and marked upregulation of β-chemokines (macrophage inhibitory proteins la and 1β and RANTES [regulated upon activation normal T-cell expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was observed in HIV-1-infected and CD40L-treated MDM relative to either infected or activated MDM alone. The addition of antibodies to RANTES or TNF-α led to a partial reversal of the CD40L-mediated inhibition of HIV-1 infection. Surface expression of CD4 and the β-chemokine receptor CCR5 was reduced on MDM in response to treatment with CD40L. In addition, treatment of CCRS-and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated inhibition of viral entry coincides with a broad range of MDM immune effector responses and the down-modulation of CCR5 and CD4 expression.

Original languageEnglish (US)
Pages (from-to)4308-4320
Number of pages13
JournalJournal of virology
Volume75
Issue number9
DOIs
StatePublished - May 17 2001

Fingerprint

CD40 Ligand
Virus Diseases
chemokines
Human immunodeficiency virus 1
Chemokines
HIV-1
macrophages
Macrophages
monocytes
infection
phagocytes
Phagocytes
T-lymphocytes
T-Lymphocytes
Chemokine Receptors
tumor necrosis factor-alpha
HIV Infections
cytokines
Up-Regulation
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

@article{57422dfb80ce47c7a6f1bb80d29f0382,
title = "Regulation of human immunodeficiency virus type 1 infection, β-chemokine production, and CCR5 expression in CD40L-stimulated macrophages: Immune control of viral entry",
abstract = "Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host immune response to human immunodeficiency virus type I (HIV.1) infection. Regulation of such immune responses can be mediated, in part, through the interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear cells during advanced HIV-1 disease has previously been reported. Based on this observation, we studied the influence of CD40L-CD40 interactions on MP effector function and viral regulation in vitro. We monitored productive viral infection, cytokine and β-chemokine production, and β-chemokine receptor expression in monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning 1 day after infection and continuing at 3-day intervals, treatment with CD40L inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A concomitant and marked upregulation of β-chemokines (macrophage inhibitory proteins la and 1β and RANTES [regulated upon activation normal T-cell expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was observed in HIV-1-infected and CD40L-treated MDM relative to either infected or activated MDM alone. The addition of antibodies to RANTES or TNF-α led to a partial reversal of the CD40L-mediated inhibition of HIV-1 infection. Surface expression of CD4 and the β-chemokine receptor CCR5 was reduced on MDM in response to treatment with CD40L. In addition, treatment of CCRS-and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated inhibition of viral entry coincides with a broad range of MDM immune effector responses and the down-modulation of CCR5 and CD4 expression.",
author = "Cotter, {R. L.} and Zheng, {Jialin C} and M. Che and Niemann, {Douglas F} and Y. Liu and J. He and E. Thomas and Gendelman, {Howard Eliot}",
year = "2001",
month = "5",
day = "17",
doi = "10.1128/JVI.75.9.4308-4320.2001",
language = "English (US)",
volume = "75",
pages = "4308--4320",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Regulation of human immunodeficiency virus type 1 infection, β-chemokine production, and CCR5 expression in CD40L-stimulated macrophages

T2 - Immune control of viral entry

AU - Cotter, R. L.

AU - Zheng, Jialin C

AU - Che, M.

AU - Niemann, Douglas F

AU - Liu, Y.

AU - He, J.

AU - Thomas, E.

AU - Gendelman, Howard Eliot

PY - 2001/5/17

Y1 - 2001/5/17

N2 - Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host immune response to human immunodeficiency virus type I (HIV.1) infection. Regulation of such immune responses can be mediated, in part, through the interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear cells during advanced HIV-1 disease has previously been reported. Based on this observation, we studied the influence of CD40L-CD40 interactions on MP effector function and viral regulation in vitro. We monitored productive viral infection, cytokine and β-chemokine production, and β-chemokine receptor expression in monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning 1 day after infection and continuing at 3-day intervals, treatment with CD40L inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A concomitant and marked upregulation of β-chemokines (macrophage inhibitory proteins la and 1β and RANTES [regulated upon activation normal T-cell expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was observed in HIV-1-infected and CD40L-treated MDM relative to either infected or activated MDM alone. The addition of antibodies to RANTES or TNF-α led to a partial reversal of the CD40L-mediated inhibition of HIV-1 infection. Surface expression of CD4 and the β-chemokine receptor CCR5 was reduced on MDM in response to treatment with CD40L. In addition, treatment of CCRS-and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated inhibition of viral entry coincides with a broad range of MDM immune effector responses and the down-modulation of CCR5 and CD4 expression.

AB - Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host immune response to human immunodeficiency virus type I (HIV.1) infection. Regulation of such immune responses can be mediated, in part, through the interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear cells during advanced HIV-1 disease has previously been reported. Based on this observation, we studied the influence of CD40L-CD40 interactions on MP effector function and viral regulation in vitro. We monitored productive viral infection, cytokine and β-chemokine production, and β-chemokine receptor expression in monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning 1 day after infection and continuing at 3-day intervals, treatment with CD40L inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A concomitant and marked upregulation of β-chemokines (macrophage inhibitory proteins la and 1β and RANTES [regulated upon activation normal T-cell expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was observed in HIV-1-infected and CD40L-treated MDM relative to either infected or activated MDM alone. The addition of antibodies to RANTES or TNF-α led to a partial reversal of the CD40L-mediated inhibition of HIV-1 infection. Surface expression of CD4 and the β-chemokine receptor CCR5 was reduced on MDM in response to treatment with CD40L. In addition, treatment of CCRS-and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated inhibition of viral entry coincides with a broad range of MDM immune effector responses and the down-modulation of CCR5 and CD4 expression.

UR - http://www.scopus.com/inward/record.url?scp=0035043330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035043330&partnerID=8YFLogxK

U2 - 10.1128/JVI.75.9.4308-4320.2001

DO - 10.1128/JVI.75.9.4308-4320.2001

M3 - Article

VL - 75

SP - 4308

EP - 4320

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

ER -