Multispecific myeloid defensins

Abstract

This review describes recent progress in our understanding of defensins and their contributions to innate immunity. Defensins are small, cysteine-rich endogenous antibiotic peptides. Human neutrophils contain large amounts of three alpha-defensins (HNP-1-HNP-3), and smaller amounts of a fourth, HNP-4. Monocytes and macrophages generally lack defensins, but they release messengers that induce the synthesis of beta-defensins in epithelial cells. In addition to their antimicrobial and immunomodulatory effects, HNP-1-HNP-3 possess antiviral and toxin-neutralizing properties. Induction of beta-defensins in epithelial cells is mediated by cell-surface Toll-like receptors or cytoplasmic peptidoglycan receptors that can recognize pathogen-associated molecules. Mutations in Nod2, a cytoplasmic peptidoglycan receptor, are associated with reduced levels of intestinal alpha-defensins and ileal Crohn's disease. Human defensin genes show marked copy-number polymorphism. High level constitutive expression of defensins may afford protection against HIV-1 and other defensin-sensitive pathogens. Theta-defensins (cyclic octadecapeptides found in nonhuman primates) have impressive antiviral and antitoxic properties. The multiple properties of defensins contribute to human innate immunity against bacteria, bacterial toxins, and viruses.