Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients

Clara Lehmann, Mark Lafferty, Alfredo Garzino-Demo, Norma Jung, Pia Hartmann, Gerd Fätkenheuer, Jeffrey S. Wolf, Jan van Lunzen, Fabio Romerio

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating plasmacytoid dendritic cells (pDC) decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNa), 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 IFNa 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 IFNa before undergoing cell death. Since IFNa 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.

Original languageEnglish (US)
Article numbere11110
JournalPloS one
Volume5
Issue number6
DOIs
StatePublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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