title: Longitudinal analysis of distribution and function of plasmacytoid dendritic cells in peripheral blood and gut mucosa of HIV infected patients.
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.
authors.affiliation: First Department of Internal Medicine.
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.forename: Katja
authors.initials: K
authors.lastname: Förster
authors.forename: Nora
authors.initials: N
authors.lastname: Koch
authors.forename: Ludger
authors.initials: L
authors.lastname: Leifeld
authors.forename: Julia
authors.initials: J
authors.lastname: Fischer
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Hans Michael
authors.initials: HM
authors.lastname: Steffen
authors.forename: Fabio
authors.initials: F
authors.lastname: Romerio
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Pia
authors.initials: P
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000473:pathology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents; D016898:Interferon-alpha
keywords: GALT; HIV; IFNα; immune activation; pDC