Cellular and Molecular Life Sciences

, Volume 68, Issue 13, pp 2215–2229 | Cite as

Paneth cell α-defensins in enteric innate immunity

  • André Joseph Ouellette
Multi-author review


Paneth cells at the base of small intestinal crypts of Lieberkühn secrete high levels of α-defensins in response to cholinergic and microbial stimuli. Paneth cell α-defensins are broad spectrum microbicides that function in the extracellular environment of the intestinal lumen, and they are responsible for the majority of secreted bactericidal peptide activity. Paneth cell α-defensins confer immunity to oral infection by Salmonella enterica serovar Typhimurium, and they are major determinants of the composition of the small intestinal microbiome. In addition to host defense molecules such as α-defensins, lysozyme, and Pla2g2a, Paneth cells also produce and release proinflammatory mediators as components of secretory granules. Disruption of Paneth cell homeostasis, with subsequent induction of endoplasmic reticulum stress, autophagy, or apoptosis, contributes to inflammation in diverse genetic and experimental mouse models.


Antimicrobial peptide Small intestine Disulfide bonds Inflammatory bowel disease Exocytosis Epithelium Dense core secretory granules Mucosa 



Antimicrobial peptide


Cysteine-rich intestinal polypeptide


Cryptdin, a term applied only to mouse Paneth cell α-defensins

(6C/A)-Crp or (6C/A)-RMAD

Peptides in which all Cys residues of the parent peptide are substituted with Ala to eliminate the disulfide array


Two cysteine-rich sequence, α-defensin-related peptide families of mice

DEFA5-transgenic (+/+)

Mice transgenic for the human Paneth cell α-defensin HD5


Endoplasmic reticulum

HD5 and HD6

Human defensin 5 and 6, the two human Paneth cell α-defensins


Human neutrophil defensin




The human cathelicidin peptide


Matrix metalloproteinase-7


Natural killer cells


Nuclear magnetic resonance


Rabbit neutrophil α-defensin


The HD5 precursor


Pancreatitis-associated protein 3 or regenerating islet-derived protein III-gamma

(R/K)-Crp or (R/K)-RMAD

Peptides in which all Arg residue positions of the parent molecule are substituted with Lys


Rhesus myeloid α-defensin


Reverse transcriptase polymerase chain reaction


Tumor necrosis factor-α



Supported by NIH Grants DK044632 and AI059346.

Supplementary material

18_2011_714_MOESM1_ESM.pdf (112 kb)
Supplementary material 1 (PDF 111 kb)
18_2011_714_MOESM2_ESM.pdf (72 kb)
Supplementary material 2 (PDF 72 kb)
18_2011_714_MOESM3_ESM.pdf (73 kb)
Supplementary material 3 (PDF 72 kb)


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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineKeck School of Medicine of the University of Southern California, USC/Norris Cancer CenterLos AngelesUSA

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