Functional role of flagellin in bacterial flagellar assembly and immune receptor activation: structure and application

Flagellin constitutes the flagellar filament that provides bacteria with locomotion and allows pathogens to invade the host tissue as a virulence factor. The N-terminal and C-terminal domains of flagellin are functionally important in filament formation and are highly conserved across diverse bacterial species. In the host, the conserved flagellin of pathogenic bacteria activates the innate immune receptors, including Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4), and functions as a pathogen-associated molecular pattern that alarms the host immune system. Recently, an array of structural studies has revealed flagellin-mediated immune receptor activation mechanisms, which can provide deep insights into the development of immune-modulating vaccines and therapeutics. In this review, we explain the biological functions and structural properties of flagellin in filament formation and immune activation and describe the application of flagellin to vaccine and drug development.