Asuspected entry route for HIV turns out to be a dead-end, report Lot de Witte, Teunis Geijtenbeek (VU University Medical Centre, Amsterdam, Netherlands), and colleagues. Langerhans cells, rather than transmitting the virus to T cells, trap HIV-1 and thus act as a barrier to infection.
The primary targets for HIV-1 invasion are CD4-expressing T cells. HIV-1 uses the CD4 receptor to gain entry. The first immune cells that HIV-1 meets in the body's mucosa, however, are a subset of dendritic cells (DCs) called Langerhans cells (LCs). Most DCs internalize HIV-1 into nonlysosomal compartments and later transmit the virus to CD4-expressing T cells in lymphoid tissues. But in LCs, the team now shows, internalization is the end of the road for HIV-1.
Binding and internalization of HIV-1 to DCs depends on C-type cell surface lectins. The team shows that, on LCs, HIV-1 associates with a C-type lectin called Langerin at the cell surface and in intracellular vesicles. Internalization via Langerin resulted in degradation of the virus and thus prevented transmission.
When the team blocked Langerin, LCs actually increased viral transmission. The LCs probably instead became infected via the small amount of CD4 these cells express. Ordinarily this CD4 route would be out-competed by the abundance of Langerin.
The fate of HIV-1 vesicles in LCs is not yet clear. It is likely that they are targeted to lysosomes for degradation. Because other DCs transmit virus via the lectin pathway, inhibitors of C-type lectins were proposed for use as microbicides. Such an approach, however, would also knock out the ability of LCs to intercept and neutralize invading HIV-1.