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Crohn’s Disease Defect Associated with Poor Response to Mycobacteria

Approximately 25 perecent of patients with Crohn’s disease have a mutation in the NOD2 gene, but until now it has not been clear how this mutation might influence the disease. Now, researchers have obtained evidence that the NOD2 protein influences the binding of mycobacteria and the subsequent launching of an immune response. Defects in NOD2 can prevent binding of the mycobacteria and allow the establishment of persistent infections. The researches showed that the NOD2 protein preferentially recognizes a peptide called N-glycolyl-MDP, which is only found in mycobacteria. When mycobacteria invade the human body, they cause an immediate and very strong immune response via the NOD2 receptor. "Now that we have a better understanding of the normal role of NOD2, we think that a mutation in this gene prevents mycobacteria from being properly recognized by the immune system," explained Dr. Marcel Behr, senior author of the report. "If mycobacteria are not recognized, the body cannot effectively fight them off and then becomes persistently infected." This new discovery associates the predisposition for Crohn's disease with both the NOD2 mutation and the presence of mycobacteria, but researchers must still determine the precise combination of these factors to understand how the disease develops. The research was published online on July 6 in the Journal of Experimental Medicine. [Press release] [JEM abstract]