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Journal of Virology, May 2005, p. 5762-5773, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5762-5773.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+ Cells in Human Rectal Mucosa

Kevin B. Gurney,1 Julie Elliott,2,3 Hoorig Nassanian,1 Carol Song,1 Elizabeth Soilleux,4 Ian McGowan,2,3 Peter A. Anton,2,3* and Benhur Lee1,3,5*

Department of Microbiology, Immunology and Molecular Genetics,1 Department of Medicine,2 UCLA AIDS Institute,3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-1489,5 Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge CB2 2XY, United Kingdom4

Received 30 June 2004/ Accepted 21 November 2004

The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+ cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ cells can bind and transfer more virus than the HLA-DR+/DC-SIGN– cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+ cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r = 0.58, P < 0.002; n = 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3ß. Thus, an increased IL-10 environment could render DC-SIGN+ cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.

* Corresponding author. Mailing address for P. A. Anton: Dept. of Medicine, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 2734 MRL, 675 Charles E. Young Dr. South, Los Angeles, CA 90095-7019. Phone: (310) 206-5797. Fax: (310) 206-8824. E-mail: Panton{at}mednet.ucla.edu.

* Corresponding author. Mailing address for B. Lee: Dept. of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA, 3825 Molecular Sciences Building, 609 Charles E. Young Drive East, Los Angeles, CA 90095-1489. Phone: (310) 794-2132. Fax: (310) 267-2580. E-mail: bLeebhL{at}ucla.edu.

Journal of Virology, May 2005, p. 5762-5773, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5762-5773.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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