Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa.
J Virol
; 79(9): 5762-73, 2005 May.
Article
en En
| MEDLINE
| ID: mdl-15827191
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Moléculas de Adhesión Celular
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Infecciones por VIH
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VIH-1
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Receptores de Superficie Celular
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Lectinas Tipo C
Límite:
Humans
Idioma:
En
Revista:
J Virol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos