Platelet–Neutrophil Interactions in Klebsiella pneumoniae Invasive Syndrome: The Role of Aspirin

Klebsiella pneumoniae invasive syndrome (KPIS), commonly originating from pyogenic liver abscesses (PLA), is delineated by metastatic infections and thrombotic complications. Diabetes mellitus (DM) remains the most significant risk factor for KPIS. Hyperglycemia exacerbates KPIS severity by promoting resistance of hypervirulent K. pneumoniae (hvKp) strains to phagocytosis and impairing neutrophil function. In light of the intricate interplay between platelet activation, inflammatory processes, and thrombotic events, patients were administered aspirin, a well-established antiplatelet agent, to diminish the incidence and recurrence of PLA in cohort studies. Platelets interact with neutrophils to form platelet-neutrophil aggregates (PNAs), might contributing to the pathogenesis of KPIS. This research examines the interactions between platelets and neutrophils under hyperglycemic conditions through in vitro assays and in vivo models of diabetic mice infected with hvKp. Elevated glucose levels significantly enhanced platelet activation, PNA formation, and bacterial viability. Salicylic acid, the active metabolite of aspirin, effectively reduced platelet activation and bacterial burden but did not inhibit PNA formation. Aspirin pre-treatment markedly improved survival rates, reduced the formation of organ abscesses, and maintained tissue integrity in diabetic mice infected with hvKp. These results highlight the intricate relationship between hyperglycemia, platelet activation, and immune dysregulation in KPIS, emphasizing aspirin as a potential adjunctive therapeutic strategy to mitigate thromboinflammatory complications associated with hvKp infection.