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Mechanisms of Disease: defensins in gastrointestinal diseases

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 406–415 (2005)Cite this article

Abstract

Defensins are endogenous antibiotics with microbicidal activity against Gram-negative and Gram-positive bacteria, fungi, viruses and protozoa. In the gastrointestinal tract, defensins help regulate the composition and number of colonizing microbes, and protect the host from food-borne and water-borne pathogens. In health, the normal host relationship with the commensal luminal microbiota is beneficial, but the same commensal bacteria could have a pathogenic role in inflammatory diseases. A disturbance in antimicrobial defense, as provided by Paneth cells of the small intestine, seems to be a critical factor in the pathogenesis of ileal Crohn's disease, an inflammatory disease of the intestinal tract. The disruption of the critical balance between antimicrobial peptides and luminal bacteria might also explain other gastrointestinal infections and diseases. Elucidating the underlying mechanisms involved in the regulation and biology of defensins could open up new therapeutic avenues.

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Figure 1: Defensin peptide and messenger RNA expression at various sites of the intestinal tract.
Figure 2: The protective role of human Paneth cell α-defensin HD5 is demonstrated in a transgenic mouse model.
Figure 3: Proposed model for the role of intestinal bacteria and host defensins in the pathogenesis and disease progression of Crohn's disease.

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Acknowledgements

JW, KF, KRH and EFS are supported by the Robert Bosch Foundation, Stuttgart, Germany. JW and CLB are supported in part by the NIH (AI 32738 and AI 50843). The authors thank many scientists in the field for valuable discussion, and apologize to those colleagues who we were unable to reference owing to space constraints.

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Authors and Affiliations

  1. junior faculty member Department of Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA

    Jan Wehkamp

  2. professor of microbiology and immunology at the Department of Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA

    Charles L Bevins

  3. senior resident Department of Internal Medicine I at the Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Klaus Fellermann

  4. senior physician Department of Internal Medicine I at the Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Klaus R Herrlinger

  5. professor of medicine and chief of the Department of Internal Medicine I at the Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Eduard F Stange

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Correspondence to Jan Wehkamp.

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Wehkamp, J., Fellermann, K., Herrlinger, K. et al. Mechanisms of Disease: defensins in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 2, 406–415 (2005). https://doi.org/10.1038/ncpgasthep0265

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