Fish soluble Toll-like receptor (TLR)5 amplifies human TLR5 response via physical binding to flagellin.
Fish has a soluble form of TLR5 ortholog (TLR5S), which does not exist in mammals. We identified TLR5S from rainbow trout and named rtTLR5S, which was about 38% homologous to the extracellular domains of human (hu) and mouse TLR5. Adjuvancy of rtTLR5S to flagellin response by human TLR5 (huTLR5) was tested in this study. A chimera constructed of rtTLR5S and the intracellular TIR of huTLR5 expressed on HeLa cells signaled the presence of various species of bacterial flagellin resulting in NK-kappaB activation. huTLR5S, when co-expressed with rtTLR5S in HeLa cells, augmented response to flagellin resulting in robust huTLR5-mediated NF-kappaB activation. Physical binding of flagellin to rtTLR5S was detected under the conditions where huTLR5 induced rtTLR5S-amplified NF-kappaB activation. Signal amplification by rtTLR5S was specific to huTLR5: no other huTLRs tested were responded to rtTLR5S. These results suggest that the soluble TLR5 serves as an adjuvant augmenting flagellin-TLR5-mediated NF-kappaB activation even in human.
Tsujita
Tadayuki
T
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
Ishii
Akihiro
A
Tsukada
Hironobu
H
Matsumoto
Misako
M
Che
Fang-Sik
FS
Seya
Tsukasa
T
D000595:Amino Acid Sequence; D000818:Animals; D005408:Flagellin / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss; D051198:Toll-Like Receptor 5 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D051198:Toll-Like Receptor 5; D005408:Flagellin