Caspase-4 and Caspase-5 Coordinate the Sensing of Streptococcus pyogenes Extracellular vesicles

Caspase-4 and caspase-5 have been linked to the sensing of Gram-negative bacteria and their extracellular vesicles (EVs). Recent studies suggested that Gram-positive bacteria can be sensed through signaling cascades involving these two caspases. In the present study, we report that S. pyogenes secretes vesicles decorated with LTA on their surface that can activate caspase-4/-5 and the NLRP3 inflammasome. We show that this sensing process depends on particle internalization and Toll-like receptor (TLR) signaling. Finally, we demonstrate that caspase-4/-5 participate in the recognition of EVs from other Gram-positive bacteria.