title: Fish soluble Toll-like receptor 5 (TLR5S) is an acute-phase protein with integral flagellin-recognition activity.
abstract: From an EST fragment of the rainbow trout that was predicted to contain leucine-rich repeats (LRR), we cloned the whole cDNA and identified a soluble form of TLR5 ortholog (rtTLR5S), which does not exist in the mouse and human. rtTLR5S was about 38% homologous to the extracellular domains of human (hu) and mouse (mo)TLR5, while rtTLR5S showed <25% homologous to those of other human or mouse TLRs. A chimera constructed of rtTLR5S and the intra-cellular TIR of huTLR5 expressed on HeLa cells signaled the presence of flagellin A and C from V. anguillarum, resulting in NF-kappaB activation. The mRNA of rtTLR5S was predominantly detected in the liver. The hepatoma cell line of the rainbow trout RTH149 that responded to flagellin, allowed to up-regulate rtTLR5S in response to V. anguillarum or its purified flagellin within 8 h. rtTLR5S, when co-expressed with membrane huTLR5 in HeLa cells, augmented huTLR5-mediated NF-kappaB activation in response to flagellin. These results, together with the genome information of the pufferfish Fugu (Fugu rubripes), suggest that in fish the soluble TLR5 is an acute-phase protein sensing bacterial infection via recognition of a variety of bacterial flagellins to augment NF-kappaB activation, and may be important for fish to survive from bacterial infection in the water.
authors.affiliation: Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Tsukada
authors.forename: Aya
authors.initials: A
authors.lastname: Fukui
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Tsujita
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Takaji
authors.initials: T
authors.lastname: Iida
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005408:Flagellin / Q000302:isolation & purification / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014733:Vibrio / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin