title: Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9.
abstract: TLRs comprise a family of evolutionary conserved sensory receptors that respond to distinct classes of ligands. For one major evolutionary branch of TLRs, the ligands are still largely unknown. Here we report the cloning and function of one member of this group, chicken TLR21 (chTLR21). This TLR is absent in the human species but has homologs in fish and frog and displays similarity with mouse TLR13. Expression of chTLR21 in HEK293 cells resulted in activation of NF-kappaB in response to unmethylated CpG DNA, typically recognized by mammalian TLR9. Silencing of chTLR21 (but not chTLR4) in chicken macrophages inhibited the response to CpG-DNA (but not to LPS), indicating similar functionality of the endogenous receptor. ChTLR21 responded to human- and murine-specific TLR9 ligands, as well as to bacterial genomic DNA isolated from Salmonella enterica serovar Enteritidis. Confocal microscopy located chTLR21 in the same intracellular compartments as human TLR9. Inhibition of the chTLR21 response by the endosomal maturation inhibitor chloroquine suggested that the receptor is functional in endolysosomes, as known for TLR9. The analogous localization and function of the phylogenetically only distantly related chTLR21 and mammalian TLR9 suggest that during evolution different classes of TLRs have emerged that recognize the same type of ligands.
authors.affiliation: Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: A Marijke
authors.initials: AM
authors.lastname: Keestra
authors.forename: Marcel R
authors.initials: MR
authors.lastname: de Zoete
authors.forename: Lieneke I
authors.initials: LI
authors.lastname: Bouwman
authors.forename: Jos P M
authors.initials: JP
authors.lastname: van Putten
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018899:CpG Islands / Q000276:immunology; D029941:Fish Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D030161:Avian Proteins; C408982:CPG-oligonucleotide; D029941:Fish Proteins; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D029867:Xenopus Proteins