Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.
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Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients. / Lehmann, Clara; Lafferty, Mark; Garzino-Demo, Alfredo; Jung, Norma; Hartmann, Pia; Fätkenheuer, Gerd; Wolf, Jeffrey S; van Lunzen, Jan; Romerio, Fabio.
in: PLOS ONE, Jahrgang 5, Nr. 6, 6, 2010, S. 11110.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.
AU - Lehmann, Clara
AU - Lafferty, Mark
AU - Garzino-Demo, Alfredo
AU - Jung, Norma
AU - Hartmann, Pia
AU - Fätkenheuer, Gerd
AU - Wolf, Jeffrey S
AU - van Lunzen, Jan
AU - Romerio, Fabio
PY - 2010
Y1 - 2010
N2 - Circulating plasmacytoid dendritic cells (pDC) decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha), which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN) of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+) T cells, thus playing into the mechanisms of AIDS immunopathogenesis.
AB - Circulating plasmacytoid dendritic cells (pDC) decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha), which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN) of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+) T cells, thus playing into the mechanisms of AIDS immunopathogenesis.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - HIV-1 isolation
KW - purification
KW - Base Sequence
KW - Flow Cytometry
KW - DNA Primers
KW - Dendritic Cells secretion
KW - HIV Infections metabolism
KW - Interferon-alpha secretion
KW - Lymph Nodes secretion
KW - Receptors, CCR7 blood
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - HIV-1 isolation
KW - purification
KW - Base Sequence
KW - Flow Cytometry
KW - DNA Primers
KW - Dendritic Cells secretion
KW - HIV Infections metabolism
KW - Interferon-alpha secretion
KW - Lymph Nodes secretion
KW - Receptors, CCR7 blood
U2 - 10.1371/journal.pone.0011110
DO - 10.1371/journal.pone.0011110
M3 - SCORING: Zeitschriftenaufsatz
VL - 5
SP - 11110
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
M1 - 6
ER -