Suilysin-induced Platelet-Neutrophil Complexes Formation is Triggered by Pore Formation-dependent Calcium Influx

Abstract

Abstract Platelet activation and platelet–neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis , an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes . Currently, S. suis –platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation. Furthermore, P-selectin released in α-granules mediated PNC formation. This process was triggered by the SLY-induced pore forming-dependent Ca 2+ influx. Moreover, we demonstrated that the Ca 2+ influx triggered an MLCK-dependent pathway playing critical roles in P-selectin activation and PNC formation, however, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signalling were not involved. Additionally, the “outside-in” signalling had a smaller effect on the SLY-induced P-selectin release and PNC formation. Interestingly, other CDCs including pneumolysin and streptolysin O have also been found to induce PNC formation in a pore forming-dependent Ca 2+ influx manner. It is possible that the bacterial CDC-mediated PNC formation is a similar response mechanism used by a wide range of bacteria. These findings may provide useful insight for discovering potential therapeutic targets for S. suis -associated STSS.