Lymphocyte-dendritic cell interactions and mucosal acquisition of SIV/HIV infection

Several previous models of HIV dissemination implicated dendritic cells as viral conduits to the lymphatics. However, recent macaque transmission and microbicide studies have highlighted a more complex situation.

Resting CD4 lymphocytes are observed to be the major infected population in mucosal tissue after vaginal challenge with SIV. Resting lymphocytes appear to bridge infection over short distances, whereas activated lymphocytes provide long-distance virus dissemination as a result of greater virus amplification. In addition, dendritic cells might be early carriers of virus, transmitting virus to T cells locally and to the lymph nodes, and thus support parallel mechanisms in transmission. Microbicide studies using agents against CCR5 corroborate a model that infection at the mucosa must occur for transmission to be successful. The fast-rate dendritic cell trafficking of virus to the lymphatics may not result in immediate and efficient viral replication in lymphatic tissue. As dendritic cells might also be infected at the mucosa before lymphatic trafficking, this would enable them to transfer virus in this region at a later timepoint.

There are now several models that can be attributed to the mucosal acquisition of SIV/HIV. One feature that unites these models is that infection in the mucosa must occur for dissemination to take place. Whether this is a feature of CD4 lymphocytes, dendritic cells or macrophage infection is still unclear. A model that intertwines one or more of the above cell types would be more prudent than addressing each in isolation.