Current status of defensins and their role in innate and adaptive immunity

Abstract

Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants. Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization. A large volume of literature is available on defensins' occurrence, structural characterization, gene expression and regulation under normal and pathological conditions. Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions. In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators.

Crucial roles of binding sites for NF-κB and C/EBPs in IκB-ζ-mediated transcriptional activation

“…A recent report has also shown critical roles for IκB-ζ in IL-1β-dependent induction of the genes [38]. Since both genes encode inducible antimicrobial proteins expressed in various epithelial tissues [39,40], one of the functions of IκB-ζ is likely to be to activate genes that play roles in elimination of infected bacteria. This concept is consistent with the observation that IκB-ζ is induced by microbial ligands of various TLRs, but not by doublestranded RNA, a ligand for TLR3, which is an intracellular receptor for RNA viruses [41].…”

Mitochondria Permeabilization by a Novel Polycation Peptide BTM-P1

“…Many membrane-active peptides have been reported to function as a defense system against bacteria in plants and animals (41)(42)(43). Among them, the positively charged peptides magainins, secreted by the skin of the am-phibia Xenopus laevis, uncouple oxidative phosphorylation and significantly inhibit respiration of rat liver mitochondria and display antimicrobial (41) and anticancer activity (21,22).…”

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

“…α-defensin To date, six HNPs have been identified [39,40,[46][47][48]. The disulphide bonds of intramolecular cysteine residues in the HNPs are 1-6, 2-4, and 3-5 linked, and consist of an intricate tertiary structure.…”

“…Besides the antibacterial activity of HNPs, other biological functions such as chemotactic activity to native resting T cells and dendritic cells, degranulation of mast cells, regulation of complement activation, and inhibition of glucocorticoid production have been implicated [45,47,[56][57][58][59].…”

“…They include being a chemotactic factor for CCR6 dendritic cells, degranulation of mast cells, and induction of the production of prostaglandin D2 [45,47,86,87].…”