Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation
Article first published online: 27 JUL 2007
Volume 65, Issue 5, pages 1147–1157, September 2007
How to Cite
Shannon, O., Hertzén, E., Norrby-Teglund, A., Mörgelin, M., Sjöbring, U. and Björck, L. (2007), Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation. Molecular Microbiology, 65: 1147–1157. doi: 10.1111/j.1365-2958.2007.05841.x
- Issue published online: 27 JUL 2007
- Article first published online: 27 JUL 2007
- Accepted 14 June, 2007.
Disturbed haemostasis is a central finding in severe Streptococcus pyogenes infection. In particular, microthrombi are found both at the local site of infection and at distant sites. Platelets are responsible for maintaining vascular function and haemostasis. We report here that M1 protein of S. pyogenes triggers immune-mediated platelet activation and thrombus formation. M1 protein is released from the bacterial surface and forms complexes with plasma fibrinogen. These complexes bind to the fibrinogen receptor on resting platelets. When these complexes also contain immunoglobulin G (IgG) against M1 protein, this will engage the Fc receptor on the platelets and activation will occur. Activation of the platelets leads to platelet aggregation and the generation of platelet-rich thrombi. Neutrophils and monocytes are in turn activated by the platelets. Platelet thrombi are deposited in the microvasculature, and aggregated platelets, IgG and M1 protein colocalize in biopsies from patients diagnosed with S. pyogenes toxic shock syndrome. This chain of events results in a pro-coagulant and pro-inflammatory state typical of severe S. pyogenes infection.