Defensins and HIV Infection

The innate immune system provides the first line of defense against a wide variety of microorganisms before the development of an adaptive immune response. Epithelial cells at mucosal surfaces and recruited leukocytes are often the first to contact microbial pathogens and mount an innate immune response including the production of Antimicrobial Peptides (AMPs) such as defensins and cathelicidins and pro-inflammatory cytokines through pattern recognition receptors (e.g. Toll-like receptors, TLRs). Defensins exhibit a broad spectrum of action against microorganisms including Grampositive and Gram-negative bacteria, fungi and viruses. In addition to their microbicidal effects they act as immunomodulators involved in inflammation, tissue repair and angiogenesis. However, increasing evidence suggests that the innate immunity including production of AMPs can act as a double-edged sword by providing protection against invading pathogens but at the same time causing potentially harmful inflammation. This review focuses on the role of defensins as innate effectors and immunodulators in HIV infection, the multiple and complex mechanisms by which defensins inhibit or enhance HIV infection in vitro as well as recent clinical evidence supporting an association between defensins and HIV transmission.