Abstract

Platelets are hematopoietic cells whose main function has for a long time been considered to be the maintenance of vascular integrity. They have an essential role in the hemostatic response, but they also have functional capabilities that go far beyond it. This review will provide an overview of platelet functions. Indeed, stress signals may induce platelet apoptosis through proapoptotis or hemostasis receptors, necrosis, and even autophagy. Platelets also interact with immune cells and modulate immune responses in terms of activation, maturation, recruitment and cytokine secretion. This review will also show that platelets, thanks to their wide range of innate immune receptors, and in particular toll-like receptors, and can be considered sentinels actively participating in the immuno-surveillance of the body. We will discuss the diversity of platelet responses following the engagement of these receptors as well as the signaling pathways involved. Finally, we will show that while platelets contribute significantly, via their TLRs, to immune response and inflammation, these receptors also participate in the pathophysiological processes associated with various pathogens and diseases, including cancer and atherosclerosis.

Highlights

  • Several platelet pattern recognition receptors (PRRs) are involved in pathogen recognition; for instance, C-type lectins comprised of the dendritic cell-specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) and C-type lectin-like receptor 2 (CLEC-2) receptors (Figure 2)

  • tolllike receptors (TLRs) are type I transmembrane proteins composed of extracellular leucine-rich repeat (LRR) motifs that mediate the recognition of PAMPs, transmembrane domains, and cytosolic Toll IL-1 receptor (TIR) endodomains that interact with the downstream adaptors required for signaling [146]

  • The team of the current study showed that the in vitro stimulation of platelets with LPS from either E. coli O111 or Salmonella minnesota, which are smooth and rough isoforms of LPS, respectively, induces the differential release by platelets of immunomodulatory molecules that trigger a differential secretion of IL-6, tumor necrosis factor (TNF)-α, and IL-8 by peripheral blood mononuclear cells [147]

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Summary

A Double-Edged Sword

Théo Ebermeyer 1 , Fabrice Cognasse 1,2 , Philippe Berthelot 3,4 , Patrick Mismetti 1,5 , Olivier Garraud 1 and Hind Hamzeh-Cognasse 1, *.

Introduction
The Central Role of Platelets in Hemostasis
Apoptosis
Necrosis
Autophagy
Platelets as Immune Cells
Release of Platelet Immunomodulatory and Antimicrobial Soluble Factors
Modulation of Immune Cell Response
Platelets as Pathogen Sensors
A Focus on Platelet TLRs
TLR Structure
TLR Signaling Pathways in Platelets
Expression and Functional Response of Platelet TLRs
Platelet Contribution to Pathogenesis through Their Innate Immunity Receptors
Sepsis
COVID-19
HIV-1 Infection
Dengue
Atherosclerosis
Cancer
Findings
Conclusions and Future Perspectives
Full Text
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