In the late nineteenth century, Paul Langerhans discovered Langerhans cells, a form of dendritic cell (DC) found on the skin. However, the term DC was first described in 1973 by Ralph M. Steinman after identifying a population of dendritic-shaped cells in the spleen of mice. Increased research on DC lead to the recognition of DCs as professional antigen presenting cells (APCs). DCs can be classified into different subsets based on their location, marker expression, immune function, and cytokine secretion. To date, four major DC subtypes have been identified: myeloid (mDCs) and plasmacytoid (pDCs) in the blood, follicular dendritic cells (FDCs) in lymph follicles, and Langerhans cells in tissues such as the skin and mucosal epithelial. DCs comprise ≤2% of total peripheralblood mononuclear cells (PBMCs). However, due to their role in the regulation of the adaptive immune response and their localization, DCs have been recognized as the first line of defense against any pathogen including Human Immunodeficiency Virus (HIV). DCs can harbor HIV and mediate its spread to other immune cells. The ability of HIV-1 to use DCs for propagation and to transfer virus to activated T cells is crucial in the early stages of HIV-1 pathogenesis. Furthermore, several research studies have been focusing on targeting HIV binding receptors on host cells such as DCs as an alternative therapeutic strategy. A major breakthrough in this research area was the discovery of a membrane associated C-type lectin, DC Specific Intercellular adhesion molecule-3 (ICAM-3) Grabbing Nonintegrin, (DC-SIGN or CD209), which facilitates HIV infection independent of the main receptor (CD4) or HIV-1 co-receptors (CCR5/CXCR4) and is classified as a novel HIV anchoring receptor that mediates viral transmission. Novel therapeutic approaches using siRNA and micro-RNA have been reported earlier to downregulate DC-SIGN and ultimately modulate the pathogen binding ability of DCs. Other approaches including the use of nanoparticles to block HIV-1 gp120 binding to DC-SIGN have also been reported. Despite all the research efforts to develop novel therapeutic approaches, HIV epidemic continues worldwide and a novel strategy to control HIV infection and its associated pathogenesis is yet to be developed. Therefore, understanding the mechanisms of interaction between DCs and HIV is crucial for the advancement of HIV research and development of novel anti-HIV therapies and vaccines. This review focuses on the latest research advances on the interactions between DCs and HIV, emphasizing the role of DC-SIGN.
