Betadefensins

Beta-defensins are a family of small, cationic antimicrobial peptides that form part of the innate immune system in vertebrates. They are produced by epithelial cells of mucosal surfaces and by some immune cells, and they exhibit broad-spectrum antimicrobial activity against bacteria, fungi, and enveloped viruses. In humans, several beta-defensin genes encode the mature peptides known as human beta-defensins (hBDs), including hBD-1, hBD-2, and hBD-3.

Structure and maturation: Beta-defensins are typically about 36 amino acids long after processing, with six conserved cysteine residues that form three disulfide bonds, yielding a compact beta-sheet-rich structure. They are synthesized as prepropeptides containing a signal sequence and a propeptide that is cleaved to release the mature peptide.

Genes and expression: The beta-defensin genes (DEFB) are organized in clusters. In humans, a prominent cluster resides on chromosome 8p23.1 and includes several DEFB genes, such as DEFB1 (hBD-1), DEFB4 (hBD-2), and DEFB103 (hBD-3). Expression is induced by microbial products and inflammatory signals; vitamin D can stimulate hBD-2 and hBD-3 in some tissues.

Mechanisms and functions: The antimicrobial action involves disruption of microbial membranes and interference with intracellular targets. Beyond direct killing, beta-defensins act as chemoattractants for CCR6-expressing immune cells and can modulate cytokine production, thus linking innate and adaptive immunity. They also show antiviral activity against several enveloped viruses.

Clinical relevance and research: Copy number variation in DEFB genes can influence susceptibility to infections and inflammatory diseases. Altered beta-defensin expression has been observed in conditions such as periodontitis and inflammatory bowel disease. Because of their broad activity and immunomodulatory properties, beta-defensins are investigated for therapeutic uses and vaccine adjuvant development.