title: Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) are important mediators of innate immunity that act mainly through secretion of interferon (IFN)-alpha. Previous studies have found that these cells can suppress HIV in vitro; additionally, pDCs have been shown to be severely reduced in the peripheral blood of HIV-infected individuals. In the present study, we sought to determine the ability of pDCs to directly suppress viral replication ex vivo and to delineate the potential mechanisms whereby pDCs are depleted in HIV-infected individuals. We demonstrate that activated pDCs strongly suppress HIV replication in autologous CD4(+) T cells via a mechanism involving IFN-alpha as well as other antiviral factors. Of note, unstimulated pDCs from infected individuals who maintain low levels of plasma viremia without antiretroviral therapy were able to suppress HIV ex vivo via a mechanism requiring cell-to-cell contact. Our data also demonstrate that death of pDCs by both apoptosis and necrosis is induced by fusion of HIV with pDCs. Taken together, our data suggest that pDCs play an important role in the control of HIV replication and that high levels of viral replication in vivo are associated with pDC cell death via apoptosis and necrosis. Elucidation of the mechanism by which pDCs suppress HIV replication in vivo may have clinically relevant implications for future therapeutic strategies.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Jennifer Hartt
authors.initials: JH
authors.lastname: Meyers
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Justement
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Eric T
authors.initials: ET
authors.lastname: Blair
authors.forename: Yongming A
authors.initials: YA
authors.lastname: Sun
authors.forename: M Angeline
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Gregg
authors.initials: G
authors.lastname: Roby
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Colin M
authors.initials: CM
authors.lastname: Kovacs
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D002470:Cell Survival / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D020869:Gene Expression Profiling; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D014779:Virus Replication / Q000276:immunology*