The Role of Human Defensins in Gastrointestinal Diseases

Jost Langhorst; Kyung-Eun Choi

Disclosures

Expert Rev Clin Immunol. 2011;7(6):779-787. 

In This Article

Abstract and Introduction

Abstract

In clarifying the pathogenesis of inflammatory bowel diseases, a dysregulation of the adaptive immune function was the main focus of research in the last decade. With increasing knowledge of antimicrobial peptides, a primary disturbed barrier function and the system of innate immunity has recently received increasing attention. Contrary to the common understanding of irritable bowel syndrome as a functional disorder, there is first evidence for an involvement of innate immunity for this condition. Peptides with high relevance seem to be the class of human defensins. This article will thus discuss current advances in immunologic research of inflammatory bowel disease and irritable bowel syndrome, focusing on defensins and their possible role as biomarkers of these diseases.

Introduction

The human immune system protects organisms with layered defenses of increasing specificity using mechanical, chemical and biological barriers. The innate immune system is the first defense line comprising all mechanisms that resist infection without specific recognition of the pathogen.[1] If pathogens successfully evade this first defense line, further adaptive immune responses are initiated. Here, the immune system adapts its response to improve its recognition of the pathogen in the future. Defense of epithelial tissues against microbial pathogens involves both acquired and innate immune responses.

In the field of inflammatory bowel diseases (IBDs) the research focus of the last decade has shifted from mainly investigating a dysregulation of the adaptive immune responses to including a primary disturbed barrier function and the system of innate immunity.[2,3] Despite colonization by, and a frequent exposure to, a variety of potential pathogenic microorganisms, intestinal infections or translocation of bacterial agents rarely occur in the GI tract and are mostly limited to highly pathogenic bacteria or predisposing disease states.[4] As a mucosal surface, the GI tract is protected by an innate antimicrobial system consisting of numerous peptides.[5] Playing an important role in host innate defence these peptides indirectly confer epithelial barrier function as an adjunct to specific immunity.[5] The class of these antimicrobial peptides (AMPs) include defensins, cathelicidine LL37 lysozyme, so called defensin-like molecules (elafin and secretory leukocyte protease inhibitor), and further protective components including mucus and trefoil factors.[4] AMPs form micropores in the phospholipid bilayer of bacterial membranes in the gut, causing loss of structural integrity and collapse of the bacterial cell.[6] This quality allows AMPs to protect the host epithelium and stem cells from virulent water-borne and food-borne pathogens and also help to regulate the number and composition of commensal microbiota.[7]

The increasing knowledge of AMPs and their role in innate immunity has added important new aspects to the current understanding of the pathogenesis of IBD.[3,8] Contrary to the common understanding of irritable bowel syndrome (IBS) as a functional disorder, innate immunity may even be relevant for this condition – at least in a subgroup of the syndrome.[9] This article will discuss current advances in immunologic research in the sections relevant for IBD and IBS with a special emphasis on defensins and their possible role as biomarkers of these diseases.

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