Platelets interact with bacterial pathogens

Abstract

Thromb Haemost 2009; 102: 613–614 The predominant role of platelets is in haemostasis. Resting platelets patrol the vasculature and become activated in response to endothelial cell damage and exposure to subendothelial matrix components, such as collagen or von Willebrand factor. Adhesion and activation result in the release of the contents of platelet granules, and in the upregulation of surface receptors for fibrinogen/fibrin and other plasma proteins. This allows firm binding between platelets to occur, resulting in aggregation and formation of platelet thrombi. Platelets may also contribute to the immune response to endovascular bacterial pathogens by releasing pro-inflammatory factors including cytokines, chemokines, and antimicrobial peptides (1). Conflicting reports exist on the role of platelets during bacterial infection. On the one hand the production of antimicrobial peptides will kill bacteria, and the release of pro-inflammatory substances and the formation of platelet-leukocyte aggregates may prime the immune response. On the other hand, the ability to bind platelets may facilitate bacterial adherence to the endothelium, and bacteria contained within a platelet plug may be protected from immune defence. In order to initiate an infection, bacteria must adhere to and multiply at normally sterile sites within the host. Many bacterial pathogens bind to host matrix proteins such as fibrinogen/fibrin, collagen, or von Willebrand factor, and since many of these host proteins are also associated with activated platelets, the platelets may represent an abundant adhesive target for bacteria. Furthermore, a number of significant Gram-positive endovascular pathogens have been shown to directly stimulate platelet activation in vitro in the absence of other agonists (2). The most well characterised interactions occur between platelets and the bacteria that cause endocarditis: Staphylococcus aureus, Streptococcus sanguis and other streptococcal species. During endocarditis, bacteria adhere to the heart valves, and a vegetation of bacteria, fibrin and platelets is formed; thereby, the ability of bacteria to activate or adhere to platelets is considered to contribute to the formation of vegetations. A number of endocarditis pathogens have been reported to bind either directly to the platelet surface or indirectly via a plasma protein bridge. Binding in itself does not mediate activation, and plasma immunoglobulin G specific for the bacterium is also required to mediate platelet activation through the Fc-receptors on the platelet surface (2). As previously mentioned, activated platelets release antibacterial peptides, which could kill the bacteria. Interestingly, it has been shown that many of the S. aureus strains isolated from endocarditis are resistant to these antibacterial peptides (3, 4). To date, platelet interactions have been mainly studied for the causative agents of endocarditis, and the results obtained may be specific for this infection. In order to elucidate the role of platelets during infection, it is important that platelet interactions are investigated for other bacterial pathogens. In a study published in this edition of Thrombosis & Haemostasis, Niemann et al have investigated the interaction between platelets and the significant human pathogen, Streptococcus pneumoniae (5). Infection with S. pneumoniae is not a significant cause of endocarditis but is a leading cause of respiratory tract infections and may cause invasive infection and septicaemia. Niemann et al report that S. pneumoniae can bind to activated platelets, and this binding is mediated by platelet bound fibrin and further stimulated by thrombospondin released from activated platelets. Platelet activation in the absence of fibrin generation, for example collagen stimulation, does not stimulate bacteria-platelet associations. Niemann et al have previously described a similar interaction of S. aureus with activated platelets and this implies that the mechanism may be conserved for significant Gram-positive pathogens (6). As previously mentioned, S. aureus can also mediate platelet activation in the absence of other agonists. The authors did not investigate the ability of S. pneumoniae to stimulate platelet activation in the absence of other agonists, and it will be interesting to determine if this significant human pathogen has, like S. aureus, multiple mechanisms to interact with platelets. The ability to adhere to activated platelets on the damaged endothelium may provide an advantage for the bacteria by protecting against killing by immune cells, which may not recognise bacterial pathogens shielded by host proteins. Alternatively, bacteria attached to a platelet aggregate may also be able to disseminate via the bloodstream to other foci. Indeed, bacteria-platelet aggregates can become sequestered in the microvasculature, contributing to the organ damage observed in septicaemia and sepsis. The contribution of thrombospondin to these bacteria-platelet associations is interesting since thrombospondin has previously been reported to bind to bacterial peptidoglycan (7). Pep© 2009 Schattauer GmbH, Stuttgart