RESUMO
Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.
Assuntos
Moléculas de Adesão Celular/fisiologia , Infecções por HIV/transmissão , HIV-1/fisiologia , Lectinas Tipo C/fisiologia , Macrófagos/virologia , Leite Humano/citologia , Receptores de Superfície Celular/fisiologia , Adulto , Especificidade de Anticorpos , Antígenos CD4/imunologia , Linhagem Celular Transformada , Feminino , Infecções por HIV/metabolismo , HIV-1/metabolismo , Humanos , Transmissão Vertical de Doenças InfecciosasRESUMO
The effects of Nef molecules on immature dendritic cells (iDCs) were analyzed using recombinant human immunodeficiency virus type 1 (HIV-1) with intact nef gene, pseudotyped with vesicular stomatitis virus glycoprotein, HIV/VSV-G/+Nef. When iDCs were infected with HIV/VSV-G/+Nef, the surface expression of CD1a, a molecule for presenting glycolipid/lipid antigens, was selectively down-regulated among CD1 molecules (CD1a, -b, -c, and -d) as well as class I MHC. Moreover, the CD1a molecules were also down-modulated and co-localized with DsRed2-tagged-Nef in CD1a-transfected cells. Their co-localization was dependent upon CD1a cytoplasmic tail and the CD1a was redistributed from cell surface to LAMP-1+ late endosomal/lysosomal compartment. These findings reveal that the HIV-1-Nef interferes with the intracellular trafficking of CD1a, and suggest the involvement of CD1a-restricted immune effectors in the protective immunity against HIV-1 infection, which implicates the feasibility of virus-derived glycolipid/lipid antigens together with epitope peptides for the vaccine development.