Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokine secretion

Platelets are currently acknowledged as cells of innate immunity and inflammation and play a complex role in sepsis. We examined whether different types of LPS have different effects on the release of soluble signaling/effective molecules from platelets. We used platelet-rich plasma from healthy volunteers and LPS from two strains of gram-negative bacteria with disparate LPS structures. We combined LPS-stimulated platelet supernatants with reporter cells and measured the PBMC cytokine secretion profiles. Upon stimulation of platelets with both Escherichia coli O111 and Salmonella minnesota LPS, the platelet LPS::TLR4 interaction activated pathways to trigger the production of a large number of molecules. The different platelet supernatants caused differential PBMC secretion of IL-6, TNFα, and IL-8. Our data demonstrate that platelets have the capacity to sense external signals differentially through a single type of pathogen recognition receptor and adjust the innate immune response appropriately for pathogens exhibiting different types of ‘danger’ signals.

► Platelets contain many immunomodulatory and inflammatory molecules. ► Platelet secretory profiles depend on the stimulus applied in vitro. ► Platelets strongly express functional TLR4. ► Various LPS stimulation of platelets can trigger secretory profiles. ► The different releasates of platelets activate PMNCs differentially.