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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 α-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.

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Figure 1: Preparation of mouse small intestinal crypts.
Figure 2: Bactericidal secretions released by Paneth cells in isolated crypts stimulated with CCh.
Figure 3: Bacterial induction of Paneth cell secretion.
Figure 5: Induction of Paneth cell secretion by bacteria and bacterial antigens.
Figure 4: Cryptdin secretion in response to CCh and bacteria.
Figure 7: Time-and dose-dependent Paneth cell secretion in response to bacteria and LPS.
Figure 6: Absence of a secretory response by Paneth cells exposed to eukaryotic pathogens.

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Acknowledgements

We thank S.B. Aley (University of Texas, El Paso) for live G. lamblia trophozoites; J.I. Gordon (Washington University School of Medicine) for CR2-tox176 transgenic mice and P. Tran for technical advice on AU-PAGE western blotting. Supported by NIH Grants DK44632 (A.J.O.), HL29594 (W.C.P.) and AI 22931 (M.E.S.) and also by Large Scale Biology Corp.(M.E.S.).

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Correspondence to Andre J. Ouellette.

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Ayabe, T., Satchell, D., Wilson, C. et al. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1, 113–118 (2000). https://doi.org/10.1038/77783

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