TLR signaling in the gut in health and disease.
The human intestine has evolved in the presence of diverse enteric microflora. TLRs convert the recognition of pathogen-associated molecules in the gut into signals for anti-microbial peptide expression, barrier fortification, and proliferation of epithelial cells. Healing of injured intestinal epithelium and clearance of intramucosal bacteria require the presence of intact TLR signaling. Nucleotide oligomerization domain (Nod)1 and Nod2 are additional pattern recognition receptors that are required for defense against invasive enteric pathogens. Through spatial and functional localization of TLR and Nod molecules, the normal gut maintains a state of controlled inflammation. By contrast, patients with inflammatory bowel disease demonstrate inflammation in response to the normal flora. A subset of these patients carry polymorphisms in TLR and CARD15/NOD2 genes. A better understanding of the delicate regulation of TLR and Nod molecules in the gut may lead to improved treatment for enteric infections and idiopathic inflammatory bowel diseases.
Abreu
Maria T
MT
Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. Maria.Abreu@mssm.edu
Fukata
Masayuki
M
Arditi
Moshe
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D001419:Bacteria / Q000276:immunology / Q000472:pathogenicity; D004751:Enteritis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D018448:Models, Immunological; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors