The Journal of Experimental Medicine
Northwestern University Inflammation Research
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Published online 21 August 2000.
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© The Rockefeller University Press, 0022-1007/2000/8/587/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 4, August 21, 2000 587-594

Brief Definitive Report

Macrophage-Tropic HIV Induces and Exploits Dendritic Cell Chemotaxis

Chen-Lung Lina, Andrew K. Sewellb, George F. Gaob,c, Kathryn T. Whelana,b, Rodney E. Phillipsb, and Jonathan M. Austyna

a Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
b Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
c Structural Molecular Biology Laboratory, Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138
Nuffield Department of Clinical Medicine, Level 7, John Radcliffe Hospital, Oxford OX3 9DU, UK.44-1865-22099344-1865-228927

asewell{at}gwmail.jr2.ox.ac.uk

Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1{alpha}, and MIP-1β. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell–derived factor (SDF)-1{alpha}. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell–tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC–T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell–specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual.

Key Words: dendritic cell • HIV • chemotaxis • chemokine • CCR5

C.-L. Lin and A.K. Sewell contributed equally to this work.

© 2000 The Rockefeller University Press


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