Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells.
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.
Fonteneau
Jean-François
JF
Institut de Biologie, INSERM U463, Nantes, France.
Larsson
Marie
M
Beignon
Anne-Sophie
AS
McKenna
Kelli
K
Dasilva
Ida
I
Amara
Ali
A
Liu
Yong-Jun
YJ
Lifson
Jeffrey D
JD
Littman
Dan R
DR
Bhardwaj
Nina
N
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
C515460:CCL19 protein, human; D039521:CD11c Antigen; D054415:Chemokine CCL19; D019742:Chemokines, CC