A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia

BackgroundPlatelets are critical cells for maintaining vascular hemostasis, but their activities in other processes are becoming apparent. Specifically, the ability of platelets to recognize and respond to infectious agents is an important area of investigation. To understand the physiologic roles of platelets invivo, most researchers have used antibody-mediated platelet depletion, which has certain limitations. ObjectiveTo develop an optimal system with which to study the contribution of platelets to protection against S.aureus blood infection. MethodsHere, we describe a novel experimental model of conditional platelet depletion based on the Cre-recombinase cell ablation system. With this technology, the simian diphtheria toxin receptor was expressed in platelet factor4-positive cells (megakaryocytes and platelets). ResultsSystemic administration of diphtheria toxin every 48h resulted in reduced platelet numbers that became undetectable after 6days. Although platelets were depleted, no other blood cells were affected. With this newly developed model, the functional contributions of platelets to protection against Staphylococcus aureus bacteremia was examined. Platelet-depleted mice succumbed to infection more rapidly than wild-type mice, and had a significantly higher bacterial burden in kidneys, elevated levels of serum markers of kidney damage, and increased levels of cytokines indicative of septic shock. ConclusionsHere, we illustrate a new mouse model for conditional platelet depletion, and implicate platelets as important participants in the immune response to bacterial blood infections.