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J Virol. 2005 May;79(9):5762-73.

Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa.

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  • 1Dept. 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, USA.

Abstract

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 3beta. 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.

PMID:
15827191
PMCID:
PMC1082722
DOI:
10.1128/JVI.79.9.5762-5773.2005
[PubMed - indexed for MEDLINE]
Free PMC Article
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