Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4.
Perturbations to the well-being of tissues in plants and invertebrates generate fragments of endogenous molecules that are recognized by innate immune receptors. Vertebrates have homologous receptors on specialized cells such as dendritic cells, but whether these receptors respond to fragments of endogenous molecules is not known. We tested the idea that Toll-like receptors on dendritic cells might recognize polysaccharide fragments of heparan sulfate proteoglycan. Dendritic cells were found to mature in response to heparan sulfate as measured by costimulatory protein expression, morphology, and T lymphocyte stimulation, but this maturation was absent when Toll-like receptor 4 was mutated or inhibited. These findings suggest that Toll-like receptors in vertebrates may monitor tissue well-being by recognizing fragments of endogenous macromolecules.
Johnson
Geoffrey B
GB
Department of Immunology, Mayo Clinic, 2-66 Medical Sciences Building, Rochester, MN 55905, USA.
Brunn
Gregory J
GJ
Kodaira
Yuzo
Y
Platt
Jeffrey L
JL
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D029721:Drosophila Proteins; D017353:Gene Deletion; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D051193:Toll-Like Receptors
C408982:CPG-oligonucleotide; D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors