Pneumococcal association to platelets is mediated by soluble fibrin and supported by thrombospondin-1

Abstract

Platelets and coagulation are involved in bacterial colonisation of the host. Streptocococcus pneumoniae (pneumococcus) are important etiologic agents of respiratory tract infections in humans. The formation of pneumococci-platelet associations may facilitate haematogenous dissemination of pneumococci by providing an adhesive surface on damaged endothelium. However, the formation of platelet-pneumococci associations and the factors involved in this process have not been described so far. The formation of platelet-pneumococci associates was analysed and quantified using flow cytometry. Binding of pneumococci to platelets was significantly increased after activation of platelets with thrombin, while platelet activation by ADP or collagen did not promote formation of platelet-pneumococci associates. In addition to be a platelet agonist, thrombin cleaves fibrinogen, which results in the generation of fibrin. The simultaneous formation of fibrin and activation of platelets was shown to be a prerequisite for a high number of platelet-pneumococci associates. Moreover, exogenously added human thrombospondin-1 (TSP-1) significantly enhanced the association of pneumococci with activated platelets. Soluble fibrin and TSP-1 are key co-factors of platelet-pneumococci-association. Similar results were recently demonstrated for S. aureus-platelet adhesion. Consequently, we hypothesise that the described mechanism of platelet-bacteria-association might represent a general and important strategy of Gram-positive bacteria during development of invasive diseases.

Endogenous Thrombospondin-1 Regulates Leukocyte Recruitment and Activation and Accelerates Death from Systemic Candidiasis

“…TSP1 has also been reported to promote pathogenesis by directly interacting with pathogenic Gram-positive bacteria including Streptococcus pneumoniae and Staphylococcus sp. [47]–[49]. More relevant to the present study, TSP1 null mice were more resistant to sepsis caused by cecal ligation or specifically by intraperitoneal inoculation of E. coli [50].…”

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

“…Interestingly, Niemann et al [97] showed that S. pneumoniae adheres to platelet aggregates and is mediated by fibrin and hTSP-1. As a result, the capability of S. pneumoniae to target platelet-bound hTSP-1 could be an important dissemination strategy during the manifestation of an invasive disease during pneumococcal infection (Fig.…”

Subterfuge and Sabotage: Evasion of Host Innate Defenses by Invasive Gram-Positive Bacterial Pathogens

“…SPN PepO protein binds plasminogen, allowing activation by urokinase-type plasminogen activator and subsequent plasmin-mediated cleavage of C3b (3). Though active plasmin can also generate fibrin, the accumulation of fibrin further prevents C3b deposition (21, 45) and additionally aids gram-positive bacteria in platelet-mediated adhesion to damaged endothelial surfaces (86a). Thus, gram-positive pathogens have evolved a repertoire of virulence factor proteins to combat the complement system.…”