Procoagulant Activity of Blood and Microvesicles Is Disturbed by Pneumococcal Pneumolysin, Which Interacts with Coagulation Factors

J Innate Immun. 2023;15(1):136-152. doi: 10.1159/000525479. Epub 2022 Jul 15.

Abstract

The coagulation and contact systems are parts of the innate immune system as they prevent bleeding and dissemination of pathogens and also contribute to microbial killing by inflammatory reactions and the release of antimicrobial peptides. Here, we investigated the influence of Streptococcus pneumoniae on the coagulation and contact system. S. pneumoniae (pneumococci), but no other investigated streptococcal species, impairs coagulation of blood by autolysis and release of pneumolysin. Defective blood coagulation results from the lysis of tissue factor-producing mononuclear cells and their procoagulant microvesicles, which are the main trigger for blood coagulation during sepsis. In addition, pneumolysin binds coagulation and contact system factors, but this does not result in activation. Thus, pneumococci modulate activation of the coagulation system by releasing pneumolysin, which could potentiate lung injury during pneumonia.

Keywords: Coagulation; Contact system; Microvesicles; Pneumolysin.

MeSH terms

  • Bacterial Proteins / metabolism
  • Blood Coagulation Factors / metabolism
  • Humans
  • Pneumococcal Infections*
  • Streptococcus pneumoniae*
  • Streptolysins / metabolism

Substances

  • plY protein, Streptococcus pneumoniae
  • Streptolysins
  • Bacterial Proteins
  • Blood Coagulation Factors

Grants and funding

This work was supported by the Federal Excellence Initiative of Mecklenburg Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF_14-BM-A55-0010_16 and ESF_14-BM-A55-0001_16) and in parts by the Deutsche Forschungsgemeinschaft (grants to SOH, project OE 547/ 4-1, and to SH, project 374031971-TRR240). Purchase of the LICOR was kindly supported by the EU-EFRE (European Funds for Regional Development) program (Registration number GHS-18-0030).