Immunodeficiency virus exploitation of dendritic cells in the early steps of infection (PDF)
Teleshova,Natalia; Frank,Ines; Pope,Melissa
Journal of Leukocyte Biology 74(5): 683-690
Publication date: 2003
The unique capacity of dendritic cells (DCs) to capture and process pathogens for presentation to the immune system, combined with their capacity to express costimulatory and adhesion molecules as well as cytokines and chemokines, renders them powerful antigen-presenting cells. However, immunodeficiency viruses hijack DCs to facilitate virus dissemination while subverting effective immune activation. Depending on the activation level of the DC subset, human immunodeficiency virus can use different receptors (CD4, chemokine, and C-type lectin receptors) to bind to DCs. These aspects likely impact whether a DC is productively infected by or simply carries virus for transmission to more permissive targets. DCs efficiently transmit virus to CD4 T cells, driving virus growth as well as providing signals to trigger virus expansion in virus-bearing CD4 T cells. There is accumulating evidence that viral determinants (nef, tat) selectively modulate immature DC biology, fostering DC-T cell interactions and virus replication without up-regulating costimulatory molecules for effective immune function. In addition, virus-loaded, immature DCs activate CD4 virus-specific T cells, and mature DCs stimulate CD4 and CD8 T cells. Thus, even if immature DCs entrap virus as it crosses the mucosae and initiate a CD4 T cell response, this is likely insufficient to control infection. Appreciating how virus modulates DC function and what determines whether virus is processed for immune stimulation or transmitted between cells will unveil the exact role of these cells in the onset of infection and advance preventative microbicide and vaccine/therapeutic approaches.
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