Temporal changes in platelet activation and organ dysfunction during invasive Streptococcus pyogenes infection

Sepsis, a severe immune response triggered by a local infection, can lead to systemic disease and collateral organ damage. Platelets, a type of immune cell, play a dual role in immune defense and organ damage during sepsis. In this study, researchers investigated the molecular, cellular, and proteome responses in a mouse model at various stages of invasive Streptococcus pyogenes infection, ranging from localized infection to systemic dissemination and inflammation.

The bacteria's entry into the bloodstream was linked to rising cytokine levels, platelet activation, and an initial increase in white blood cells, which later declined. By analyzing various organ functions using plasma biomarkers, histopathological changes, and protein reorganization, the researchers identified distinct temporal patterns of organ dysfunction.

Initially, platelets were mobilized to the skin infection, but later accumulated in the liver, aligning with the organ damage caused by sepsis. The study demonstrated that Streptococcus pyogenes binds to the GPIB receptor on platelets in vitro, indicating that bacteria may attach to platelets in the bloodstream. Treating infected mice with antibiotics decreased bacterial levels, reduced sepsis-induced organ damage, and partially reversed the disease-associated protein changes in both plasma and liver.

However, administering ticagrelor, a drug that blocks platelet activation, did not worsen the disease nor provide significant protection against sepsis-induced organ damage. Interestingly, at the proteome level, ticagrelor effectively reversed sepsis-induced platelet activation and stress responses in the liver. The researchers conclude that platelets contribute to liver dysfunction in sepsis and may serve as a potential target for adjunct therapy in combination with antibiotics.