Projects per year
Abstract
Toll-like receptor 5 (TLR5) recognition of flagellin instigates inflammatory signalling. Significant sequence variation in TLR5 exists between animal species but its impact on activity is less well understood. Building on our previous research that bovine TLR5 (bTLR5) is functional, we compared human and bovine TLR5 activity and signalling in cognate cell lines. bTLR5 induced higher levels of CXCL8 when expressed in bovine cells and reciprocal results were found for human TLR5 (hTLR5) in human cells, indicative of host cell specificity in this response. Analysis of Toll/interleukin-1 receptor (TIR) sequences indicated that these differential responses involve cognate MyD88 recognition. siRNA knockdowns and inhibitor experiments demonstrated that there are some host differences in signalling. Although, PI3K activation is required for bTLR5 signalling, mutating bTLR5 F798 to hTLR5 Y798 within a putative PI3K motif resulted in a significantly reduced response. All ruminants have F798 in contrast to most other species, suggesting that TLR5 signalling has evolved differently in ruminants. Evolutionary divergence between bovine and human TLR5 was also apparent in relation to responses measured to diverse bacterial flagellins. Our results underscore the importance of species specific studies and how differences may alter efficacy of TLR-based vaccine adjuvants.
Original language | English |
---|---|
Pages (from-to) | 17677 |
Journal | Scientific Reports |
Volume | 7 |
Issue number | 1 |
DOIs | |
Publication status | Published - 15 Dec 2017 |
Keywords / Materials (for Non-textual outputs)
- Journal Article
Fingerprint
Dive into the research topics of 'Host species adaptation of TLR5 signalling and flagellin recognition'. Together they form a unique fingerprint.Projects
- 4 Finished
-
ISP 2 2017/22 Control of Infectious Diseases
Gally, D. (Principal Investigator)
1/04/17 → 31/03/22
Project: Research
-
Defining the molecular basis of H7 flagellin as an adhesin and mucosal adjuvant for vaccine
Gally, D. (Principal Investigator) & Mahajan, A. (Co-investigator)
1/04/14 → 30/09/15
Project: Research
-
Innate immunity and endemic diseases in livestock species
Collie, D. (Principal Investigator), Beard, P. (Co-investigator), Bishop, S. (Co-investigator), Bronsvoort, M. (Co-investigator), Burt, D. (Co-investigator), Fitzgerald, R. (Co-investigator), Freeman, T. (Co-investigator), Gally, D. (Co-investigator), Gill, A. (Co-investigator), Glass, E. (Co-investigator), Hocking, P. (Co-investigator), Hope, J. (Co-investigator), Hume, D. (Co-investigator), Kaiser, P. (Co-investigator), Mabbott, N. (Co-investigator), McLachlan, G. (Co-investigator), Morrison, L. (Co-investigator), Stevens, J. (Co-investigator), Stevens, M. (Co-investigator) & Watson, M. (Co-investigator)
1/04/12 → 31/03/17
Project: Research