Toll-Like Receptor 5 Activation in Innate Immune Responses
Summary
Toll-like receptor 5 (TLR5) is a membrane-bound sensor of the innate immune system that detects flagellin, a conserved protein component of bacterial flagella. Upon flagellin recognition, TLR5 dimerises and recruits the adaptor molecule MyD88, triggering a signalling cascade that leads to activation of nuclear transcription factors such as NF-κB and AP-1. This process results in the rapid release of proinflammatory cytokines, chemokines and antimicrobial peptides at sites of microbial invasion. Structurally, flagellin engages TLR5 via a hot-spot on its D1 domain, with contributions from the D0 region to stabilise the signalling complex. Evolutionary variation in TLR5 across species can alter ligand specificity and signalling efficiency, yet the core interaction remains remarkably conserved. Activation of TLR5 not only mediates local barrier defence in tissues such as gut and lung epithelium but also shapes adaptive immunity by promoting dendritic cell maturation and subsequent T cell responses. Exploitation of this natural adjuvant function has underpinned the development of flagellin-based vaccine platforms and immunotherapies, while ongoing structural and functional studies inform strategies to enhance efficacy, limit reactogenicity and overcome potential immunogenicity of the carrier molecule. Emerging data highlight the global significance of TLR5 as a target for novel anti-infective, vaccine and inflammatory disease interventions.
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Toll-Like Receptor 5 Activation in Innate Immune Responses publication trend
The graph below shows the total number of articles in toll-like receptor 5 activation in innate immune responses across all publications each year (not limited to Nature Index journals).
Technical terms
Toll-like receptor 5 (TLR5): A pattern recognition receptor on host cells that detects bacterial flagellin and initiates an immune response.
Flagellin: The principal protein of bacterial flagella that serves as the natural ligand for TLR5.
MyD88: An intracellular adaptor protein that couples TLR5 activation to downstream signalling pathways.
Adjuvant: A compound that enhances the immune response to an antigen when administered together.
References
- Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity. npj Vaccines (2023).
- Deimmunization of flagellin adjuvant for clinical application. Current Opinion in Virology (2023).
- Recombinant Domain of Flagellin Promotes In Vitro a Chemotactic Inflammatory Profile in Human Immune Cells Independently of a Dendritic Cell Phenotype. Molecules (2023).
- A conserved TLR5 binding and activation hot spot on flagellin. Scientific Reports (2017).
- The role of the C-terminal D0 domain of flagellin in activation of Toll like receptor 5. PLOS Pathogens (2017).
- Host species adaptation of TLR5 signalling and flagellin recognition. Scientific Reports (2017).
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