Defensin

Defensins are small, cysteine-rich antimicrobial peptides that form part of the innate immune system in plants, animals, and some fungi. They are grouped into families, with alpha- and beta-defensins present in humans and theta-defensins in some primates; plant defensins constitute a distinct lineage. Examples include human neutrophil peptides (HNP-1 to HNP-4), Paneth cell defensins (HD5, HD6), and beta-defensins (hBD-1 to hBD-4).

Defensins are typically 2–6 kDa in size and are stabilized by multiple disulfide bonds, yielding a compact, protease-resistant structure. They are produced by epithelial cells and granulocytes such as neutrophils and can be secreted to mucosal surfaces or released from granules during inflammation. Plant defensins are expressed broadly in plant tissues and share the cysteine-stabilized motif.

Defensins exhibit broad antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, and some enveloped viruses. Their primary mechanism involves electrostatic attraction to negatively charged microbial membranes, followed by membrane disruption and pore formation. Some defensins can enter cells to affect intracellular targets and also modulate host responses, including chemotaxis and cytokine production.

Expression of defensins is induced by infection and inflammatory signals and contributes to barrier defense and shaping of the microbiota. In humans, altered defensin levels have been linked to inflammatory bowel disease and increased susceptibility to infections, highlighting their importance in mucosal immunity and host defense.

Defensins are studied as potential therapeutics and as templates for new antimicrobials. Plant defensins have agricultural and pharmaceutical interest due to antifungal properties. Ongoing research addresses their regulation, spectrum of activity, and the emergence of resistance or tolerance in pathogens.