Functional analysis of bovine TLR5 and association with IgA responses of cattle following systemic immunisation with H7 flagella
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- 作者：Amin Tahoun (1) (2)
- 刊名：Veterinary Research
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：46
- 期：1
- 全文大小：1,907 KB
- 参考文献：1. D枚ring G, Meisner C, Stern M, Flagella Vaccine Trial Study Group (2007) Double-blind randomized placebo-controlled phase III study of a / Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients. Proc Natl Acad Sci U S A 104:11020鈥?1025 rnal" href="http://dx.doi.org/10.1073/pnas.0702403104" target="_blank" title="It opens in new window">CrossRef
- 刊物主题：Veterinary Medicine;
- 出版者：BioMed Central
- ISSN：1297-9716
文摘
Flagellin subunits are important inducers of host immune responses through activation of TLR5 when extracellular and the inflammasome if cytosolic. Our previous work demonstrated that systemic immunization of cattle with flagella generates systemic and mucosal IgA responses. The IgA response in mice is TLR5-dependent and TLR5 can impact on the general magnitude of the adaptive response. However, due to sequence differences between bovine and human/murine TLR5 sequences, it is not clear whether bovine TLR5 (bTLR5) is able to stimulate an inflammatory response following interaction with flagellin. To address this we have examined the innate responses of both human and bovine cells containing bTLR5 to H7 flagellin from E. coli O157:H7. Both HEK293 (human origin) and embryonic bovine lung (EBL) cells transfected with bTLR5 responded to addition of H7 flagellin compared to non-transfected controls. Responses were significantly reduced when mutations were introduced into the TLR5-binding regions of H7 flagellin, including an R90T substitution. In bovine primary macrophages, flagellin-stimulated CXCL8 mRNA and secreted protein levels were significantly reduced when TLR5 transcript levels were suppressed by specific siRNAs and stimulation was reduced with the R90T-H7 variant. While these results indicate that the bTLR5 sequence produces a functional flagellin-recognition receptor, cattle immunized with R90T-H7 flagella also demonstrated systemic IgA responses to the flagellin in comparison to adjuvant only controls. This presumably either reflects our findings that R90T-H7 still activates bTLR5, albeit with reduced efficiency compared to WT H7 flagellin, or that other flagellin recognition pathways may play a role in this mucosal response.