HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway

Jiaxiang Ji, Gautam K. Sahu, Vivian L. Braciale, Miles W. Cloyd

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14+ monocytes infected by either HIV-1213 (X4) or HIV-1BaL (R5) produced IL-10, IL-6, tumor necrosis factor-α (TNF-α), and to a lesser extent, IFN-γ. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14+ monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-α and IFN-γ but no IL-10 production by CD14+ monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1213, HIV-1BaL or HIV-1 gp160 in CD14+ monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1213 could induce IL-10 mRNA expression in CD14+ monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1213-induced IL-10 mRNA expression in CD14+ monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14+ monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.

Original languageEnglish (US)
Pages (from-to)729-736
Number of pages8
JournalInternational Immunology
Volume17
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Interleukin-10
HIV-1
Monocytes
HIV
CD4 Antigens
Cytokines
Goats
Messenger RNA
Interleukin-6
Tumor Necrosis Factor-alpha
Human Immunodeficiency Virus Proteins
Immunosuppressive Agents
Virus Replication
HIV Infections

Keywords

  • CD4-independent
  • HIV-1
  • IL-10
  • Monocytes

ASJC Scopus subject areas

  • Immunology

Cite this

HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway. / Ji, Jiaxiang; Sahu, Gautam K.; Braciale, Vivian L.; Cloyd, Miles W.

In: International Immunology, Vol. 17, No. 6, 06.2005, p. 729-736.

Research output: Contribution to journalArticle

Ji, Jiaxiang ; Sahu, Gautam K. ; Braciale, Vivian L. ; Cloyd, Miles W. / HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway. In: International Immunology. 2005 ; Vol. 17, No. 6. pp. 729-736.
@article{4a706d8de66a425aa087c19fd747aa2d,
title = "HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway",
abstract = "In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14+ monocytes infected by either HIV-1213 (X4) or HIV-1BaL (R5) produced IL-10, IL-6, tumor necrosis factor-α (TNF-α), and to a lesser extent, IFN-γ. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14+ monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-α and IFN-γ but no IL-10 production by CD14+ monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1213, HIV-1BaL or HIV-1 gp160 in CD14+ monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1213 could induce IL-10 mRNA expression in CD14+ monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1213-induced IL-10 mRNA expression in CD14+ monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14+ monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.",
keywords = "CD4-independent, HIV-1, IL-10, Monocytes",
author = "Jiaxiang Ji and Sahu, {Gautam K.} and Braciale, {Vivian L.} and Cloyd, {Miles W.}",
year = "2005",
month = "6",
doi = "10.1093/intimm/dxh252",
language = "English (US)",
volume = "17",
pages = "729--736",
journal = "International Immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway

AU - Ji, Jiaxiang

AU - Sahu, Gautam K.

AU - Braciale, Vivian L.

AU - Cloyd, Miles W.

PY - 2005/6

Y1 - 2005/6

N2 - In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14+ monocytes infected by either HIV-1213 (X4) or HIV-1BaL (R5) produced IL-10, IL-6, tumor necrosis factor-α (TNF-α), and to a lesser extent, IFN-γ. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14+ monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-α and IFN-γ but no IL-10 production by CD14+ monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1213, HIV-1BaL or HIV-1 gp160 in CD14+ monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1213 could induce IL-10 mRNA expression in CD14+ monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1213-induced IL-10 mRNA expression in CD14+ monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14+ monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.

AB - In HIV-infected patients, increased levels of IL-10, mainly produced by virally infected monocytes, were reported to be associated with impaired cell-mediated immune responses. In this study, we investigated how HIV-1 induces IL-10 production in human monocytes. We found that CD14+ monocytes infected by either HIV-1213 (X4) or HIV-1BaL (R5) produced IL-10, IL-6, tumor necrosis factor-α (TNF-α), and to a lesser extent, IFN-γ. However, the capacity of HIV-1 to induce these cytokines was not dependent on virus replication since UV-inactivated HIV-1 induced similar levels of these cytokines. In addition, soluble HIV-1 gp160 could induce CD14+ monocytes to produce IL-10 but at lower levels. Cross-linking CD4 molecules (XLCD4) with anti-CD4 mAbs and goat anti-mouse IgG (GAM) resulted in high levels of IL-6, TNF-α and IFN-γ but no IL-10 production by CD14+ monocytes. Interestingly, neither anti-CD4 mAbs nor recombinant soluble CD4 (sCD4) receptor could block IL-10 secretion induced by HIV-1213, HIV-1BaL or HIV-1 gp160 in CD14+ monocytes, whereas anti-CD4 mAb or sCD4 almost completely blocked the secretion of the other cytokines. Furthermore, HIV-1213 could induce IL-10 mRNA expression in CD14+ monocytes while XLCD4 by anti-CD4 mAb and GAM failed to do so. As with IL-10 protein levels, HIV-1213-induced IL-10 mRNA expression in CD14+ monocytes could not be inhibited by anti-CD4 mAb or sCD4. Taken together, HIV-1 binding to CD14+ monocytes can induce CD4-independent IL-10 production at both mRNA and protein levels. This finding suggests that HIV induces the immunosuppressive IL-10 production in monocytes and is not dependent on CD4 molecules and that interference with HIV entry through CD4 molecules may have no impact on counteracting the effects of IL-10 during HIV infection.

KW - CD4-independent

KW - HIV-1

KW - IL-10

KW - Monocytes

UR - http://www.scopus.com/inward/record.url?scp=26444522325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26444522325&partnerID=8YFLogxK

U2 - 10.1093/intimm/dxh252

DO - 10.1093/intimm/dxh252

M3 - Article

VL - 17

SP - 729

EP - 736

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 6

ER -