Immature dendritic cells (DCs) located in peripheral mucosal tissues continually monitor for invading microorganisms. Using an expansive array of pattern recognition receptors including Toll-like receptors and C-type lectins DCs capture and internalize invading pathogens and process them for presentation on MHC. Certain pathogens including HIV have evolved mechanisms to subvert the normal antigen presentation function of DCs to allow survival in the host and efficient infection of CD4 T cells. DC-SIGN, a C-type lectin present on DCs has been shown to bind HIV gp120 and enhanced infection of CD4 T cells. Despite a wealth of data indicating that DC-SIGN can account for the capture and potentiation effect of DCs on HIV infection, our preliminary data and other reports indicate additional receptors must play a role in this complex process This study will determine the mechanism by which DCs enhance HIV infection of T cells. We will stimulate DC subsets with a variety of signals through different Toll like receptors and ask whether specific maturation signals are required to render DCs efficient in potentiating HIV infection. In concert with these experiments we will examine the ability of different subsets of DC to capture HIV virions and for their ability to internalize and present virions at the immunological synapse. In support of these efforts we will employ established molecular and immunological techniques to identify novel molecules expressed on DCs that interact with HIV. Understanding the proteins on DC which capture and potentiate HIV infection will lead to new and more effective vaccine strategies for HIV.
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