Fig. 1: Bacterial PSAs transduce signals through innate receptors to modulate immune responses.

TLR1/2 and Dectin-1 mediate PSA-induced PI3K activation, which leads to CREB-dependent transcription of anti-inflammatory genes in dendritic cells. This signaling pathway might drive dendritic cells to differentiate T cells into IL-10-producing cells. The LOS portion of PSA can bind to TLR4 and activate the MyD88-dependent NF-kB signaling pathway and the TRIF-dependent IRF3 signaling pathway, leading to the transcription of proinflammatory cytokines (e.g., IFN-β).