Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria

Abstract

Paneth cells in mouse small intestinal crypts secrete granules rich in microbicidal peptides when exposed to bacteria or bacterial antigens. The dose-dependent secretion occurs within minutes and alpha-defensins, or cryptdins, account for 70% of the released bactericidal peptide activity. Gram-negative bacteria, Gram-positive bacteria, lipopolysaccharide, lipoteichoic acid, lipid A and muramyl dipeptide elicit cryptdin secretion. Live fungi and protozoa, however, do not stimulate degranulation. Thus intestinal Paneth cells contribute to innate immunity by sensing bacteria and bacterial antigens, and discharge microbicidal peptides at effective concentrations accordingly.

NF-κB and the immune response

“…TLR ligation is at least partly responsible for the NF-kB-dependent expression of defensinscationic peptides that exert direct bactericidal activity by inducing membrane permeabilization. Small intestinal Paneth cells, for example, release large amounts of a-defensins into the intestinal lumen following exposure to a variety of bacteria/bacterial products (Ayabe et al, 2000). The production of antimicrobial nitrogen and oxygen species, which are acutely toxic to a variety of microbes, augments the activity of antimicrobial peptides.…”

Efficacy of Cryptdin-2 as an Adjunct to Antibiotics from Various Generations Against Salmonella

“…Among naturally occurring AMPs, defensins form a unique and principle family of cysteine rich cationic polypeptides with 3 or 4 disulfide bridges [6]. Mouse enteric alpha-defensins called cryptdins are expressed in the granules of Paneth cells and are secreted into the lumen of intestinal crypts in response to bacterial stimuli [7]. Cryptdins are broad-spectrum AMPs due to their ability to kill various bacteria [8][9][10], parasites [11] and enveloped viruses [12] in vitro.…”

Starvation Compromises Paneth Cells

“…1 These cells sense bacterial presence and secrete granules containing antimicrobial peptides, including lysozyme, RegIII␥, and cryptdins (the murine counterparts of human ␣-defensins) both constitutively and in response to activation by bacteria or their products. 2 Using a murine cell ablation model, Paneth cells were shown to be crucial in host protection against invasion of both commensal and pathogenic microbiota. 3 In addition, our group has recently shown the additive importance of Paneth cells in preventing bacterial translocation in situations of physical intestinal barrier loss.…”