Longitudinal analysis of distribution and function of plasmacytoid dendritic cells in peripheral blood and gut mucosa of HIV infected patients

Clara Lehmann, Norma Jung, Katja Förster, Nora Koch, Ludger Leifeld, Julia Fischer, Stefan Mauss, Uta Drebber, Hans Michael Steffen, Fabio Romerio, Gerd Fätkenheuer, Pia Hartmann

Research output: Contribution to journalArticlepeer-review

Abstract

Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.

Original languageEnglish (US)
Pages (from-to)940-949
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number6
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • GALT
  • HIV
  • IFNα
  • immune activation
  • pDC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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