Mechanisms and regulation of defensins in host defense

Abstract

As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.

Balancing Act of the Intestinal Antimicrobial Proteins on Gut Microbiota and Health

“…They bind to cell membranes, forming transmembrane pores, permeabilizing the membrane, and reducing bacterial viability. Detailed mechanistic models regarding defensin-mediated transmembrane pore formation are discussed elsewhere (Fu et al, 2023 ; Ganz, 2003 ).…”

Enhancing Recognition and Interpretation of Functional Phenotypic Sequences through Fine-Tuning Pre-Trained Genomic Models

“…During the selection phase for Highly_Specific_Gene intervals, we noted that olfactory receptor and defensin family genes exhibit distinct tissue-specific protein expression patterns [20,21]. Consequently, we extracted defensin family genes from the genome annotation file (Gencode.v43), merged intervals within 10 kb using Bedtools Merge, and then divided them into 1 kb sections as Defensins regions with Bedtools Makewindows.…”

Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents

“…NETs are extracellular web-like structures of DNA-histone complexes with neutrophil granule proteins such as defensins [ 5 ]. In 1985, human neutrophil defensins (human neutrophil peptides 1-3, HNP1-3) were discovered by Lehrer [ 6 ]. They are mainly synthesized by neutrophils, epithelial cells, and Paneth cells [ 6 ].…”

“…In 1985, human neutrophil defensins (human neutrophil peptides 1-3, HNP1-3) were discovered by Lehrer [ 6 ]. They are mainly synthesized by neutrophils, epithelial cells, and Paneth cells [ 6 ]. To date, six human defensins have been detected [ 7 ].…”

“…Mammalian defensins are classified as alpha- and beta-defensins [ 9 ]. Human alpha-defensins are located on chromosome 8 [ 6 ]. Structurally, they are a family of small peptides (less than 10 kDa) [ 10 ].…”