Overview
Defensins are small (29–45 amino acid) cationic antimicrobial peptides that form the first line of chemical defense at mucosal surfaces. Alpha-defensins (HD5, HD6) are produced by Paneth cells in the small intestinal crypts; beta-defensins (hBD1-4) are produced by epithelial cells throughout the gut. Defensins kill bacteria by membrane disruption and are regulated by microbial signals — making them a key interface between innate immunity and the microbiome.
Key Functions
- Antimicrobial: Electrostatic attraction to negatively charged bacterial membranes → pore formation → cell lysis. Effective against Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses.
- Microbiome shaping: Defensins selectively kill sensitive organisms while sparing resistant commensals — actively shaping community composition.
- HD6 net formation: Alpha-defensin HD6 forms nanotrap structures that physically entangle bacteria, preventing mucosal penetration.
Crohn's Disease
Reduced Paneth cell alpha-defensin expression (particularly HD5) is a hallmark of ileal Crohn's disease, enabling pathobiont invasion of the crypt epithelium haag 2015 intestinal microbiota innate immunity crohns. NOD2 mutations (the strongest CD genetic risk factor) impair defensin induction.
Cross-References
- innate immunity — defensins as chemical barrier defense
- crohns disease — reduced defensin expression in ileal CD
- vitamin d — calcitriol induces cathelicidin (related antimicrobial peptide)
- calprotectin — complementary antimicrobial protein