title: Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells.
abstract: In this study, we analyzed the phenotypic and physiological consequences of the interaction of plasmacytoid dendritic cells (pDCs) with human immunodeficiency virus type 1 (HIV-1). pDCs are one cellular target of HIV-1 and respond to the virus by producing alpha/beta interferon (IFN-alpha/beta) and chemokines. The outcome of this interaction, notably on the function of bystander myeloid DC (CD11c+ DCs), remains unclear. We therefore evaluated the effects of HIV-1 exposure on these two DC subsets under various conditions. Blood-purified pDCs and CD11c+ DCs were exposed in vitro to HIV-1, after which maturation markers, cytokine production, migratory capacity, and CD4 T-cell stimulatory capacity were analyzed. pDCs exposed to different strains of infectious or even chemically inactivated, nonreplicating HIV-1 strongly upregulated the expression of maturation markers, such as CD83 and functional CCR7, analogous to exposure to R-848, a synthetic agonist of toll-like receptor-7 and -8. In addition, HIV-1-activated pDCs produced cytokines (IFN-alpha and tumor necrosis factor alpha), migrated in response to CCL19 and, in coculture, matured CD11c+ DCs, which are not directly activated by HIV. pDCs also acquired the ability to stimulate naïve CD4+ T cells, albeit less efficiently than CD11c+ DCs. This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses.
authors.affiliation: Institut de Biologie, INSERM U463, Nantes, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fonteneau
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Beignon
authors.forename: Kelli
authors.initials: K
authors.lastname: McKenna
authors.forename: Ida
authors.initials: I
authors.lastname: Dasilva
authors.forename: Ali
authors.initials: A
authors.lastname: Amara
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D039521:CD11c Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000502:physiology; D002633:Chemotaxis; D003713:Dendritic Cells / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans
chemical_list: C515460:CCL19 protein, human; D039521:CD11c Antigen; D054415:Chemokine CCL19; D019742:Chemokines, CC