Bacteria-induced intracellular signalling in platelets

Abstract

Multiple studies have now shown that various species of bacteria can stimulate platelets; many in a strain and donor-dependent manner. The signalling pathways underlying this platelet activation has been the subject of scrutiny for the last decade. The best-delineated pathway is that in response to Streptococcal species, such as Streptococcus sanguinis (S. sanguinis), Streptococcus gordonii (S. gordonii) and Streptococcus oralis (S. oralis), where a pathway is initiated by the engagement of the low affinity IgG receptor, FcγRIIA. This leads to and involves the tyrosine kinase Syk, the adaptor protein Linker of Activated T Cells (LAT) and subsequently both phospholipase Cγ2 (PLCγ2) and phosphatidylinositol-3-kinase (PI-3-K). Finally, this leads to the expression of the αIIbβ3 integrin, the synthesis and release of thromboxane A₂ (T × A₂) and the exocytosis of PF4, each of which plays a crucial role in secondary signalling and full platelet activation. Roles for other signalling pathways in Streptococcal-induced platelet activation are less clear, although an ADP-mediated inhibition of adenylyl cyclase, a glycoprotein Ib/IX/V-mediated pathway and perhaps a complement-induced pathway have each been proposed. Platelet activation by Porphyromonas gingivalis (P. gingivalis) at least partially shares the FcγRIIA/Syk/PLCγ2/PI-3-K mechanism utilised by Streptococcal species. However, it has also been suggested that P. gingivalis activates platelets by two additional methods; stimulation of the protease-activated receptors leading to activation of phospholipase Cβ (PLCβ), and the engagement of Toll-like receptors 2 and 4 by released lipopolysaccharide leading to an ill-defined pathway which may involve PI-3-K. Consequently, it appears that bacteria can stimulate platelets by eliciting multiple signalling pathways some of which are common, and some unique, to individual species.

• Bacillus
• bacteria
• platelets
• Porphyromonas
• signalling
• Streptococcus

Acknowledgements

The author acknowledges, with thanks, Dr Sara Israels for helpful discussion during the preparation, and for critical reading, of this paper.

Declaration of interest

The author reports no declaration of interest.