Suilysin-induced Platelet-Neutrophil Complexes Formation is Triggered by Pore Formation-dependent Calcium Influx.
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 Ca2+influx. Moreover, we demonstrated that the Ca2+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 Ca2+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.
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.|Department of clinical laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China.
Shengwei
S
Zhang
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Yuling
Y
Zheng
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Shaolong
S
Chen
Department of clinical laboratory, Beijing You'an hospital, Capital Medical University, Beijing 100069, China.
Shujing
S
Huang
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Keke
K
Liu
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Qingyu
Q
Lv
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Yongqiang
Y
Jiang
State key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Yuan
Y
Yuan
D001792:Blood Platelets / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D020013:Calcium Signaling; D002448:Cell Adhesion; D006460:Hemolysin Proteins / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D015398:Signal Transduction; D017011:Streptococcus suis / Q000502:physiology*
D006460:Hemolysin Proteins; D019007:P-Selectin; C546937:SELP protein, human; C104760:suilysin