Invasive Streptococcus pneumoniae trigger platelet activation via Toll-like receptor 2

Sepsis is the most common manifestation of invasive pneumococcal disease and is characterized by a severe systemic inflammatory state that leads to circulatory compromise or end organ malperfusion or dysfunction. Patients suffering from sepsis often display low platelet counts characterized by thrombocytopenia as a result of platelet activation.

To investigate the mechanism through which platelets become activated in sepsis upon binding to Streptococcus pneumoniae.

We determined S. pneumoniae inducible platelet reactivity using light transmission aggregometry. Dense granule secretion was measured by luminometry using a luciferin/luciferase assay.

Streptococcus pneumoniae induced platelet aggregation in a strain-dependent manner. Induction of aggregation was not attributable to capsule serotype, as unencapsulated strains also induced platelet aggregation. Platelet aggregation was not associated with pneumolysin toxin, as a pneumolysin-deficient mutant of S. pneumoniae induced aggregation equally as well as the parent strain. Platelet aggregation also occurred in the absence of plasma proteins or antibody, and was GPIIbIIIa dependent but aspirin independent. Toll-like receptor 2 (TLR2) is present on platelets and acts as a receptor for gram-positive bacterial lipoteichoic acid and peptidoglycan. Inhibition of TLR2 but not TLR4 (also present on platelets) completely abolished platelet aggregation. S. pneumoniae-induced platelet aggregation resulted in activation of the PI3kinase/RAP1 pathway, leading to integrin GPIIbIIIa activation and dense granule release.

Our results demonstrate a novel interaction between S. pneumoniae and TLR2, which results in platelet activation that is likely to contribute to the thrombotic complications of sepsis.