NOD proteins are intracellular sensors of infections that recognize cell wall or peptidoglycan components of many bacteria. The importance of these sensors in maintaining homeostasis in the intestine is indicated by the consequences for individuals lacking one of these sensors, NOD2. Specifically, NOD2 mutations have been found in a large percentage of individuals with a form of inflammatory bowel disease known as Crohn's disease. How might the absence of NOD2 lead to loss of barrier integrity and thus to increased inflammation in the gastrointestinal epithelium?

Question

Quizplus · Accepted Answer

The Answer is NOD2 binds to peptidoglycan that is released from the gut microbiota and then signals to activate the transcription factor NF

\kappa

B. NF

\kappa

B activation leads to production of inflammatory cytokines and chemokines, antimicrobial peptides and mucin. This is considered a healthy, steady-state level of inflammation, that serves to restrain the microbiota, create physical separation between the microbes and the gut epithelial cells, and leads to enhanced barrier function. In Crohn's disease that is associated with NOD2 mutations, this process breaks down and the intestinal barrier is compromised. While the details of these changes are not fully known, the outcome of chronic inflammation likely reflects increased stimulation of the immune cells in the gut epithelium by over-exposure to commensal or pathogenic microbes.

NOD Proteins Are Intracellular Sensors of Infections That Recognize Cell