The roles of antimicrobial peptides in innate host defense

Abstract

Antimicrobial peptides (AMPs) are multi-functional peptides whose fundamental biological role in vivo has been proposed to be the elimination of pathogenic microorganisms, including Gram-positive and -negative bacteria, fungi, and viruses. Genes encoding these peptides are expressed in a variety of cells in the host, including circulating phagocytic cells and mucosal epithelial cells, demonstrating a wide range of utility in the innate immune system. Expression of these genes is tightly regulated; they are induced by pathogens and cytokines as part of the host defense response, and they can be suppressed by bacterial virulence factors and environmental factors which can lead to increased susceptibility to infection. New research has also cast light on alternative functionalities, including immunomodulatory activities, which are related to their unique structural characteristics. These peptides represent not only an important component of innate host defense against microbial colonization and a link between innate and adaptive immunity, but also form a foundation for the development of new therapeutic agents.

Fig. (1). Magainin and mechanisms of purported pore formation

1A. α-helical host defense peptide, magainin. Hydrophobic residues are green, basic residues are blue. 1B. Carpet model as AMP blanket the membrane building up charge differential. 1C. Barrel stave model as AMP permeate the membrane disallowing the flip-flop of phospholipids between the leaflets. 1D. The toroidal pore method that allows the phospholipids membrane to flip flop, caused by bending of the lipids, and segregating them into micelles.

Fig. (2). Gene structure for human α-defensins (A), β-defensins (B) and cathelicidin (C)

The general structure for each family is shown with exon numbers for the genes, the 5′ and 3′ Untranslated Regions (UTRs) for the mRNA, and the precursor regions for the peptides.