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 [1]. 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