TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not TLR7

Chao Yang Lai, Yi Ling Liu, Guann Yi Yu, Ming Chei Maa, Tzeng Horng Leu, Congfeng Xu, Yunping Luo, Rong Xiang, Tsung Hsien Chuang

研究成果: Article同行評審

12 引文 斯高帕斯(Scopus)

摘要

Toll-like receptors 7 (TLR7) and 8 (TLR8) recognize viral single-stranded RNA and small molecular weight agonists to activate anti-viral immune responses. TLR8s from different species have distinct ligand recognitions. For example, human TLR8 is responsive to ligand stimulation, but mouse and rat TLR8 are activated by small molecular weight agonists only in the presence of polyT-oligodeoxynucleotides. TLR7 and TLR8 have been reported to be absent and pseudogenized, respectively, in rabbit (. Oryctolagus cuniculus). In this study, we detected the expression of rabbit (rab)TLR8 in immune-cell-associated tissues. Cell proliferation and cytokine expressions in rabbit splenocytes were induced by the TLR7/8 ligand but not by the TLR7 ligands, suggesting that rabTLR8 is functional but rabTLR7 is not. In rabbits, CL075, a TLR7/8 ligand, activated an antigen-specific antibody response, although one not as potent as aluminum salt or Freund's adjuvant. Nevertheless, CL075, alone or in combination with aluminum salt, generates fewer adverse effects than Freund's adjuvant at the injection sites. To further investigate the activation of rabTLR8, we cloned its cDNA. In cell-based assay, this rabTLR8 is activated by TLR7/8 ligand but not activated by TLR7 ligand. Upon stimulation the rabTLR8 had a lower activation compared to the activation of TLR8 from other species, except the mouse and rat TLR8s. Using different deletion and human-rabbit chimeric TLR8 expressing constructs, we showed that an extra peptide in the undefined region results in reduced activity of rabTLR8. These results provide a molecular basis for the mild activities of TLR7/8 ligands in rabbits, and suggest TLR7/8 agonists may provide safer immune stimuli in rabbits than in other non-rodent species.

原文English
頁(從 - 到)5593-5599
頁數7
期刊Vaccine
32
發行號43
DOIs
出版狀態Published - 2014 九月 29

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 免疫學與微生物學 (全部)
  • 獸醫 (全部)
  • 公共衛生、環境和職業健康
  • 傳染性疾病

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