Pili are long, thin, hair-like structures found on the surface of many bacteria. In human pathogen Group A Streptococcus (GAS), the pilus structure plays an important role in adhesion and host colonisation. GAS pilus has long been recognised as an important virulence factor and a promising vaccine candidate for GAS infection. While current research mostly focuses on pilus function and vaccine potential, there is a lack of knowledge on how the host immune system recognises and responds to this abundant surface structure. We explored the interaction between GAS pili and components of the innate immune system. Using recombinant forms of pilus proteins and Lactococcus lactis gain-of-function strains expressing GAS pili in immunoassays and flow cytometry experiments, we found that pili mediated interaction with toll-like receptors (TLRs), cytokine production, and immune cell activation. Further experiments indicated that pili mediated inflammation stimulated antibody production in mice and did not correlate with disease severity in wax worms.
The GAS pilus proteins were shown to be highly immunostimulatory ligands of TLR2, with the ability to prime the immune system for enhanced antibody production. The insight gained into the immunomodulatory characteristics of GAS pili emphasise the pilus proteins’ potential as a GAS vaccine candidate and as an adjuvant in other vaccine formulations.