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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

Abstract

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.

Keywords

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

Abbreviations

AMP

Antimicrobial peptide

CRIP

Cysteine-rich intestinal polypeptide

Crp

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

CRS1C, CRS4C

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

DEFA5-transgenic (+/+)

Mice transgenic for the human Paneth cell α-defensin HD5

ER

Endoplasmic reticulum

HD5 and HD6

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

HNP

Human neutrophil defensin

IL-17

Interleukin-17

LL-37

The human cathelicidin peptide

MMP7

Matrix metalloproteinase-7

NK

Natural killer cells

NMR

Nuclear magnetic resonance

NP-

Rabbit neutrophil α-defensin

proHD5

The HD5 precursor

RegIII-γ

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

RMAD

Rhesus myeloid α-defensin

RT-PCR

Reverse transcriptase polymerase chain reaction

TNF-α

Tumor necrosis factor-α

Notes

Acknowledgments

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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