Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.
Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
Rakoff-Nahoum
Seth
S
Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Paglino
Justin
J
Eslami-Varzaneh
Fatima
F
Edberg
Stephen
S
Medzhitov
Ruslan
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D001419:Bacteria / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D003106:Colon / Q000276:immunology / Q000293:injuries / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D007109:Immunity / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000293:injuries / Q000382:microbiology*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D013559:Symbiosis / Q000276:immunology*; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D006360:Heat-Shock Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors