Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Table 1 Antimicrobial peptides in the gastrointestinal tract

Antimicrobial peptide class	Gene	Specific antimicrobial peptides	Tissue expression	Biologic function
α-defensins (human neutrophil peptides)[5-9]	DEFA	Human defensin 5 and 6 (HD5 and HD6)	Paneth cells	Confers resistance to oral challenge with enteric pathogens, regulates the intestinal microbiota by reducing levels of segmented filamentous bacteria, restricts infection by limiting intestinal epithelial cell invasion
β-defensins[5,10-13]	DEFB	Human β-defensins 1–4 (hBD-1, hBD-2, hBD-3, and hBD-4)	Intestinal epithelial cells	Antimicrobial activity (hBD-2-4) against bacterial pathogens including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes, antimicrobial activity (hBD-1) against gram-positive commensals
Cathelicidin[14-22]	CAMP	Cathelicidin (LL-37/hCAP18)	Colonic epithelial cells, neutrophils, monocytes, macrophages, mast cells	Cationic peptide that directly disrupts bacterial cell membranes, deficiency increases susceptibility to infection with enterohemorrhagic E. coli (EHEC)
Regenerating (Reg) protein[23-29]	REG	RegIII; Hepatocarcinoma-intestine pancreas (HIP)/pancreatitis-associated protein (PAP)	Paneth cells, intestinal epithelial cells	Regulates intestinal homeostasis by maintaining a physical separation between epithelial cells and the microbiota, selective for gram-positive bacteria through interaction with cell wall peptidoglycan
Lactoferrin[30]	LTF	Lactoferrin	Epithelial cells	Secreted iron binding protein, sequesters free iron required for bacterial growth
Lipocalin[31,129]	LCN2	Lipocalin-2 (neutrophil gelatinase-associated lipocalin, GAL)	Neutrophils, granulocytes, macrophages, epithelial cells	Binds to bacterial siderophore enterobactin and inhibits bacterial growth by sequestering iron
Calprotectin[32]	S100A8, S100A9	Calprotectin	Intestinal epithelial cells, neutrophils	Chelates and sequesters metal co-factors (manganese, zinc, iron) during infection and inhibits bacterial growth
Hepcidin[33]	HAMP, LEAP1	Hepcidin antimicrobial peptide	Intestinal epithelial cells	Regulates iron absorption and homeostasis, inhibits bacterial growth by limiting iron availability
Galectin[34,35]	LGALS	Galectin-3, Galectin-4, Galectin-8	Intestinal epithelial cells	Galectins has bactericidal activity against bacteria expressing blood group antigen, Gal-8 targets damaged vesicles for autophagy during bacteria invasion
Lysozyme[36]	LYZ	Lysozyme	Paneth cells	Enzymatic degradation of bacterial membranes, preference towards Gram-positive pathogens
Elafin[37]	PI3	Elafin (peptidase inhibitor 3)	Intestinal epithelial cells	Binds to bacterial lipopolysaccharide (LPS) and modulates innate immunity
Secretory Leukocyte Protease Inhibitor (SLPI)[38,39]	SLPI	SLPI	Intestinal epithelial cells, paneth cells, neutrophils, macrophages	Protease inhibitor binds to bacterial mRNA and DNA, dose-dependent bactericidal properties of SLPI against both Gram-positive and Gram-negative bacteria, has fungicidal properties