Role of toll-like receptors in spontaneous commensal-dependent colitis.
Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and its commensal microflora. Heterogeneity of disease susceptibility in humans and rodents suggest that multiple mechanisms are responsible for the etiology of IBD. In particular, deficiencies in anti-inflammatory and immune-suppressive mechanisms play an important role in the development of IBD. However, it is unknown how the indigenous microflora stimulates the immune system and how this response is regulated. To address these questions, we investigated the role of Toll-like receptor (TLR) signaling in the development of spontaneous, commensal-dependent colitis in interleukin (IL)-2- and IL-10-deficient mice. We report that colitis was dependent on TLR signaling in Il10(-/-) mice. In contrast, Il2(-/-) mice developed intestinal inflammation in the absence of TLR signaling pathways. These results demonstrate a differential role of innate immune recognition by TLRs in the development of commensal-dependent colitis.
Rakoff-Nahoum
Seth
S
Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Hao
Liming
L
Medzhitov
Ruslan
R
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D003092:Colitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D007376:Interleukin-2; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D016753:Interleukin-10