Streptococci and Platelets - A Study of Host-Pathogen Interaction Dynamics

Sammanfattning: Invasive infections remains one of the leading causes of death due to infections over the world, and efficient treatment remains elusive. One of the major causes of sepsis and other invasive infections is pathogenic streptococci that cause a wide range of clinical manifestations in humans. Group A and group G streptococci have both been shown to cause both infections of milder ranges as well as severe invasive infections. Pathogenic streptococci have been shown to exhibit immune modulatory and immune evasion properties allowing for survival in the human host, even in the most hostile niches, such as the blood. Dissemination through the circulation would allow for interactions with several blood cells, among them platelets. In this thesis we have aimed to further elucidate the interactions between platelets and both group A streptococci (GAS) and group G streptococci (GGS), which may occur during sepsis. This would in turn add to the knowledge of the pathogenesis of invasive infections. In paper I we showed that the interactions between group A streptococci and human platelets led to platelet activation and aggregation as well as a temporary entrapment of bacteria in the platelet aggregates. The temporary entrapment of bacteria were shown to be due to active dis-aggregation by the bacteria and which factor we attempted to identify in paper II. The bacterial factor responsible for the previously seen dis-aggregation was deemed complex and most likely multi-factorial. In paper III we attempted to elucidate the effects of platelet interactions with bacteria on leukocytes. We could show that group A streptococci is able to modulate leukocyte function through the interactions with platelets and that the previously seen dis-aggregation of platelet aggregates no longer occurred. Lastly in paper IV we investigated the interactions between both human and murine platelets and group G streptococci, where we determined that platelet aggregation occurs in a fibrinogen dependent manner and that it may contribute to bacterial dissemination. Our combined results show that platelet activation and aggregation occur in response to both group A and G streptococci and that these interactions may allow for increased bacterial survival and dissemination.