When an organism, such a bacterium or virus, invades mucosal tissues, a primary line of defense is binding of the invading organism by antigen-presenting dendritic cells which internalize the organism by phagocytosis and digest it. The dendritic cells move to the T cell-rich lymph nodes where peptides on the dendritic cell surface are presented to the T cell in association with MHC antigens.  

The interaction of the dendritic cells with the T4 cells in the lymph nodes results from the presence of a receptor protein called DC-SIGN (Dendritic Cell (DC)-Specific Intercellular adhesion molecule 3 (ICAM-3) Grabbing Non-integrin). This allows the dendritic cells to bind a protein called ICAM-3 on the surface of resting T cells and brings the dendritic cell and the T cell into close apposition required for T-cell receptor engagement and antigen presentation. 

In an HIV infected person, dendritic cells accumulate the virus particles on their surfaces but usually do not internalize them. Interaction of dendritic cells with HIV occurs via binding of HIV gp120 to DC-SIGN which has a higher affinity for gp120 than CD4 antigen. The dendritic cells carry the virus to the lymph nodes resulting in efficient infection of CD4+ T cells. It also appears that when bound to the dendritic cell surface, the HIV virions retain their infectivity longer than when free in the circulation, that is days rather than hours. This concentration of HIV on the dendritic cell surface is important as early in infection, the number of virus particles may be very low and experiments with very low numbers that mimic the situation in the patient show that CD4 expressing T cells are not infected in the absence of DC-SIGN on the dendritic cells. 

The binding site for DC-SIGN on gp120 is not the same as its binding site for ICAM-3 and so the dendritic cell can still interact with the T cell. It might also be possible to interfere with dendritic cell-HIV interactions without blocking dendritic cell-T cell interactions.  

Dendritic cell co-receptors

Immature dendritic cells express the CCR5 chemokine receptor (characteristic of macrophages – the HIV subtypes that infect the patient via mucosal surfaces are macrophage-tropic).  After binding antigen, the dendritic cell matures and its CCR5 is replaced by another chemokine receptor, CXCR4 which is characteristic of T4 cells. Notably, immature dendritic cells migrate towards HIV that binds to macrophages (expressing CCR5) but not T4 cell-binding HIV (that bind CXCR4). The binding of HIV to the CCR5-expressing dendritic cells could result in a productive infection because these cells also express CD4 antigen but it is possible that DC-SIGN binding stops internalization of the virus into the dendritic cell. 

Thus, HIV uses dendritic cells in the surface mucosa for transport to regions of the body containing large numbers of its target cells, the T4 CD4+ helper cells. Infection of the T4 cell may be aided by syncytium formation between the dendritic cell and the T4 cell.