Host-microbe interaction: mechanisms of defensin deficiency in Crohn's disease.
Defensins are endogenous antibiotics with microbicidal activity against Gram-negative and -positive bacteria, fungi, enveloped viruses and protozoa. A disturbed antimicrobial defense, as provided by Paneth and other epithelial cell defensins, seems to be a critical factor in the pathogenesis of Crohn's disease, an inflammatory disease of the intestinal tract. Different direct and indirect mechanisms leading to a breakdown of antimicrobial barrier function include direct changes in defensin gene numbers (e.g., copy number polymorphism), genetic mutations in pattern-recognition receptors (e.g., nucleotide-binding oligomerization domain 2) and, as described recently, a differentiation problem of epithelial stem cells mediated by the wingless type (Wnt) pathway. Knowledge regarding the regulation and biology of defensins provides an attractive target to open up new therapeutic avenues.
Institute of Clinical Pharmacology, Dr Margarete Fischer-Bosch Institute and University of Tübingen, Auerbachstr. 112, 70376 Stuttgart, Germany. guoxing.wang@ikp-stuttgart.de
Guoxing
G
Wang
Eduard F
EF
Stange
Jan
J
Wehkamp
D000818:Animals; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D023082:Defensins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000254:growth & development / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D019879:Paneth Cells / Q000378:metabolism; D011110:Polymorphism, Genetic; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism
D023082:Defensins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051153:Wnt Proteins