Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.
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.
Lehmann
Clara
C
Institute of Human Virology, University of Maryland, Baltimore, Maryland, United States of America.
Lafferty
Mark
M
Garzino-Demo
Alfredo
A
Jung
Norma
N
Hartmann
Pia
P
Fätkenheuer
Gerd
G
Wolf
Jeffrey S
JS
van Lunzen
Jan
J
Romerio
Fabio
F
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D054400:Receptors, CCR7 / Q000097:blood
C515370:CCR7 protein, human; D017931:DNA Primers; D016898:Interferon-alpha; D054400:Receptors, CCR7