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.
