The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Abstract 

Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the TLRs expressed on platelets and megakaryocytes and how these receptors affect the function of these cells. Through TLRs, platelets go beyond hemostatic regulation and play a pivotal role in inflammation and infection.

Abbreviations: TLR, toll-like receptor, NFκB, nuclear factor kappa B, MAPK, mitogen activated protein kinase, PAMP, pathogen associated molecular patterns, LPS, lipopolysaccharide, TIR, toll/interleukin-1 receptor, MyD88, myeloid differentiation primary response gene 88, IRAK1/4, interleukin-1 receptor associated kinase 1/4, TRAF6, tumor necrosis factor associated factor 6, LTA, lipoteichoic acid, WT, wildtype, ALS, anaphylaxis-like shock, PAF, platelet activating factor, TNF-α, tumor necrosis factor α, IL6, interleukin 6, COX-2, cyclooxygenase-2, PGE₂, prostaglandin E₂, sCD40L, soluble CD40 ligand, RANTES, regulated upon activation, normal T cell expressed and secreted, PDGF-AB, platelet-derived growth factor-AB, EHEC, enterohemorrhagic E. coli, NO, nitric oxide, cGMP, cyclic guanosine monophosphate, PKG, protein kinase G, ATP, adenosine triphosphate, PAR-1, protease activated receptor-1, PI3K, phosphoinositide 3 kinase, ROS, reactive oxygen species, ERK1/2, extracellular signal related kinase 1/2, FXIIIa, factor XIII activated, PBP, platelet binding protein, PF4, platelet factor-4

Keywords: Platelets, Toll-like Receptors, Megakaryocytes, TLR2, TLR4