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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Fish soluble Toll-like receptor (TLR)5 amplifies human TLR5 response via physical binding to flagellin
Tadayuki Tsujita1, Akihiro Ishii, Hironobu Tsukada
1Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
Abstract:
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.
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