Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells.
Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.
Sanders
Rogier W
RW
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
de Jong
Esther C
EC
Baldwin
Christopher E
CE
Schuitemaker
Joost H N
JH
Kapsenberg
Martien L
ML
Berkhout
Ben
B
D002450:Cell Communication; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000821:virology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1