Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

Jeffrey A. Martinson; Alejandro Roman-Gonzalez; Allan R. Tenorio; Carlos J. Montoya; Carolyne N. Gichinga; Maria T. Rugeles; Mark Tomai; Arthur M. Krieg; Smita Ghanekar; Linda L. Baum; Alan L. Landay

doi:10.1016/j.cellimm.2008.01.007

Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

Jeffrey A. Martinson, Alejandro Roman-Gonzalez, Allan R. Tenorio, Carlos J. Montoya, Carolyne N. Gichinga, Maria T. Rugeles, Mark Tomai, Arthur M. Krieg, Smita Ghanekar, Linda L. Baum, Alan L. Landay

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

Abstract

We compared TLR responsiveness in PBMC from HIV-1-infected and uninfected individuals using the TLR agonists: TLR7 (3M-001), TLR8 (3M-002), and TLR7/8 (3M-011). Activation and maturation of plasmacytoid dendritic cells (pDC) were measured by evaluating CD86, CD40, and CD83 expression and myeloid dendritic cell (mDC) activation was measured by evaluating CD40 expression. All agonists tested induced activation and maturation of pDC in PBMC cultures of cells from HIV⁺ and HIV^- individuals. The TLR7 agonist induced significantly less pDC maturation in cells from HIV⁺ individuals. Quantitative assessment of secreted IFN-α and pro-inflammatory cytokines at the single cell level showed that pDC from HIV⁺ individuals stimulated with TLR7 and TLR7/8 induced IFN-α. TLR8 and TLR7/8 agonists induced IL-12 and COX-2 expression in mDC from HIV⁺ and HIV^- individuals. Understanding pDC and mDC activation and maturation in HIV-1 infection could lead to more rational development of immunotherapeutic strategies to stimulate the adaptive immune response to HIV-1.

Original language	English (US)
Pages (from-to)	75-84
Number of pages	10
Journal	Cellular Immunology
Volume	250
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cellimm.2008.01.007
State	Published - Nov 2007
Externally published	Yes

Keywords

COX-2
Dendritic cells
Human immunodeficiency virus
Interferon-alpha
Pro-inflammatory cytokines
Toll-like receptor 7
Toll-like receptor 8
Toll-like receptor agonists

ASJC Scopus subject areas

Immunology

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10.1016/j.cellimm.2008.01.007

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title = "Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands",

abstract = "We compared TLR responsiveness in PBMC from HIV-1-infected and uninfected individuals using the TLR agonists: TLR7 (3M-001), TLR8 (3M-002), and TLR7/8 (3M-011). Activation and maturation of plasmacytoid dendritic cells (pDC) were measured by evaluating CD86, CD40, and CD83 expression and myeloid dendritic cell (mDC) activation was measured by evaluating CD40 expression. All agonists tested induced activation and maturation of pDC in PBMC cultures of cells from HIV+ and HIV- individuals. The TLR7 agonist induced significantly less pDC maturation in cells from HIV+ individuals. Quantitative assessment of secreted IFN-α and pro-inflammatory cytokines at the single cell level showed that pDC from HIV+ individuals stimulated with TLR7 and TLR7/8 induced IFN-α. TLR8 and TLR7/8 agonists induced IL-12 and COX-2 expression in mDC from HIV+ and HIV- individuals. Understanding pDC and mDC activation and maturation in HIV-1 infection could lead to more rational development of immunotherapeutic strategies to stimulate the adaptive immune response to HIV-1.",

keywords = "COX-2, Dendritic cells, Human immunodeficiency virus, Interferon-alpha, Pro-inflammatory cytokines, Toll-like receptor 7, Toll-like receptor 8, Toll-like receptor agonists",

author = "Martinson, {Jeffrey A.} and Alejandro Roman-Gonzalez and Tenorio, {Allan R.} and Montoya, {Carlos J.} and Gichinga, {Carolyne N.} and Rugeles, {Maria T.} and Mark Tomai and Krieg, {Arthur M.} and Smita Ghanekar and Baum, {Linda L.} and Landay, {Alan L.}",

year = "2007",

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language = "English (US)",

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AU - Martinson, Jeffrey A.

AU - Roman-Gonzalez, Alejandro

AU - Tenorio, Allan R.

AU - Montoya, Carlos J.

AU - Gichinga, Carolyne N.

AU - Rugeles, Maria T.

AU - Tomai, Mark

AU - Krieg, Arthur M.

AU - Ghanekar, Smita

AU - Baum, Linda L.

AU - Landay, Alan L.

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AB - We compared TLR responsiveness in PBMC from HIV-1-infected and uninfected individuals using the TLR agonists: TLR7 (3M-001), TLR8 (3M-002), and TLR7/8 (3M-011). Activation and maturation of plasmacytoid dendritic cells (pDC) were measured by evaluating CD86, CD40, and CD83 expression and myeloid dendritic cell (mDC) activation was measured by evaluating CD40 expression. All agonists tested induced activation and maturation of pDC in PBMC cultures of cells from HIV+ and HIV- individuals. The TLR7 agonist induced significantly less pDC maturation in cells from HIV+ individuals. Quantitative assessment of secreted IFN-α and pro-inflammatory cytokines at the single cell level showed that pDC from HIV+ individuals stimulated with TLR7 and TLR7/8 induced IFN-α. TLR8 and TLR7/8 agonists induced IL-12 and COX-2 expression in mDC from HIV+ and HIV- individuals. Understanding pDC and mDC activation and maturation in HIV-1 infection could lead to more rational development of immunotherapeutic strategies to stimulate the adaptive immune response to HIV-1.

KW - COX-2

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KW - Toll-like receptor 8

KW - Toll-like receptor agonists

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Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

Abstract

Keywords

ASJC Scopus subject areas

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