Robert I Lehrer1. 1. David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. rlehrer@mednet.ucla.edu
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: The multiple properties of defensins contribute to human innate immunity against bacteria, bacterial toxins, and viruses.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: The multiple properties of defensins contribute to human innate immunity against bacteria, bacterial toxins, and viruses.
Authors: Guangshun Wang; Karen M Watson; Alan Peterkofsky; Robert W Buckheit Journal: Antimicrob Agents Chemother Date: 2010-01-19 Impact factor: 5.191
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