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Journal of Virology, May 2004, p. 5223-5232, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5223-5232.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic Cells

Jean-François Fonteneau,^1, Marie Larsson,^2, Anne-Sophie Beignon,² Kelli McKenna,² Ida Dasilva,² Ali Amara,³ Yong-Jun Liu,⁴ Jeffrey D. Lifson,⁵ Dan R. Littman,³ and Nina Bhardwaj^2*

Institut de Biologie, INSERM U463, Nantes, France,¹ Departments of Medicine and Pathology,² Howard Hughes Medical Institute and Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York,³ Department of Immunology and Center for Cancer Immunology Research, MD Anderson Cancer Center, University of Texas, Houston, Texas,⁴ AIDS Vaccine Program, SAIC/Frederick, Inc., National Cancer Institute, Frederick, Maryland⁵

Received 13 November 2003/ Accepted 21 January 2004

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-/ß) 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- 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.

J.-F.F. and M.L. contributed equally to this work.

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