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Antimicrobial Peptides in Inflammatory Bowel Disease

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Crohn's Disease and Ulcerative Colitis

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Abstract

Antimicrobial peptides are one of the most ancient forms of host defense in nature. In the mammalian intestine, clear and compelling evidence supports that antimicrobial peptides play two fundamental roles: protection from enteric pathogens and shaping the composition of the colonizing microbiota. These functions likely hold relevance to host–microbe interactions that underlie inflammatory bowel disease (IBD) pathogenesis. Epithelial cells of the human intestine express a collection of antimicrobial peptides that have overlapping and complementary activities. These peptides have substantial influence on the intestinal microbiota. Prevailing theories on the pathogenesis of IBD invoke a role for the detrimental effects of intestinal microbes in the initiation and/or propagation of mucosal inflammation. The most abundant antimicrobial peptides in the human intestine are α(alpha)-defensin peptides, most notably human defensin (HD)-5 and HD6. Other abundant polypeptides, which are larger in size but with fundamentally similar physiological roles, are lysozyme, secretory phospholipase A2, and the C-type lectin RegIIIα(alpha). Specialized epithelial cells named Paneth cells produce and secrete vast quantities of these various antimicrobial peptides. Evidence supports that reduced Paneth cell α(alpha)-defensin expression may be a key factor in the pathogenesis of ileal Crohn’s disease, a subgroup of IBD. Furthermore, several susceptibility genes for IBD may manifest their effects, in part, through compromise of Paneth cell antimicrobial peptide production or function. For example, the microbial sensor NOD-2, the autophagy protein ATG16L1, the endoplasmic reticulum stress responder XBP-1, the calcium-dependent potassium channel KCa3.1 and the transcription factor TCF4 are all important in Paneth cell function. While not proven, it is likely that the Paneth cell dysfunction, which may result from variants in genes encoding these or other Paneth cell proteins, may substantially contribute to IBD pathogenesis.

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  1. Department of Microbiology and Immunology, University of California, Davis School of Medicine, Davis, CA, 95616, USA

    Charles L. Bevins MD, PhD

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  1. Charles L. Bevins MD, PhD
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Correspondence to Charles L. Bevins MD, PhD .

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  1. Medical School of the Humboldt Universit, Department of Medicine, Charité Medical Center, Virchow Hospita, Berlin, 13344, Germany

    Daniel C. Baumgart

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Bevins, C.L. (2012). Antimicrobial Peptides in Inflammatory Bowel Disease. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0998-4_8

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