Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa.
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.
Gurney
Kevin B
KB
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, USA.
Elliott
Julie
J
Nassanian
Hoorig
H
Song
Carol
C
Soilleux
Elizabeth
E
McGowan
Ian
I
Anton
Peter A
PA
Lee
Benhur
B
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D006684:HLA-DR Antigens; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D037181:Lectins, C-Type / Q000378:metabolism*; D009068:Movement; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000821:virology; D015854:Up-Regulation; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D016753:Interleukin-10; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin