Nucleotide-binding-oligomerization domain proteins and toll-like receptors: sensors of the inflammatory bowel diseases' microbial environment.
OBJECTIVE
Chronic inflammatory bowel diseases appear to result from inappropriate immune responses driven by apparently normal intestinal microflora in genetically susceptible hosts. This review focuses on recently described mechanisms balancing toll-like receptor and nucleotide-binding-oligomerization domain activation in the face of ubiquitous enteric flora.


RESULTS
Toll-like receptor and nucleotide-binding-oligomerization domain signaling plays an integral role in the close collaboration between the intestinal epithelial cell monolayer and adjacent mucosal immune cells. Pathways activated by functional cytosolic nucleotide-binding-oligomerization domain proteins appear to interact with those mediated by membrane-associated toll-like receptors in the innate and adaptive immune defense against intra-and extracellular pathogens. Nucleotide-binding-oligomerization domain-mediated signaling may also control toll-like receptor-induced proinflammatory pathways.


CONCLUSIONS
Intersections between toll-like receptor and nucleotide-binding-oligomerization domain pathways may exist to refine the host immune response to pathogens and prevent undesired immune stimulation driven by the intestinal microbiota. Deficient toll-like receptor and nucleotide-binding-oligomerization domain function due to genetic variability is associated with an increased susceptibility to the development of inflammatory bowel disease.
Mueller
Tobias
T
Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Podolsky
Daniel K
DK
D001419:Bacteria / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors