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Platelets and the immune continuum

Key Points

  • Platelets have a plethora of soluble and cell-associated immunomodulatory molecules that can enhance and in some instances inhibit immune responses in a variety of diverse settings.

  • Platelets are naturally adhesive and can interact with various cells of the innate and adaptive immune system.

  • Platelets store preformed and synthesized immunomodulatory molecules that can markedly affect immune responses. These molecules include transforming growth factor-β, interleukin-1, platelet-derived growth factor and CC-chemokine ligand 5 (also known as RANTES).

  • Platelets express and secrete CD40 and CD154 and are the largest source of soluble CD154, which can affect both dendritic cell maturation and T cell activation.

  • Platelets express Toll-like receptors and actively bind to microorganisms, and in some instances can be directly cytopathic against bacteria. This, together with their large numbers within the circulation, makes them the ultimate bacterial sentinels in the bloodstream.

  • Platelets have been shown to have a central role in the pathogenesis of a diverse array of immune-mediated and infectious diseases, such as atherosclerosis, sepsis-induced lung damage, rheumatoid arthritis and malaria.

Abstract

Platelets are anucleate cells that are crucial mediators of haemostasis. Most immunologists probably don't think about platelets every day, and may even consider these cells to be 'nuisances' in certain in vitro studies. However, it is becoming increasingly clear that platelets have inflammatory functions and can influence both innate and adaptive immune responses. Here, we discuss the mechanisms by which platelets contribute to immunity: these small cells are more immunologically savvy than we once thought.

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Figure 1: Platelet functions in haemostasis.
Figure 2: The structure of a platelet.
Figure 3: Three typical examples of how activated platelets can mediate cell–cell interactions and affect innate immune responses.
Figure 4: TLR4+ platelets mediate pulmonary neutrophil activation during sepsis.
Figure 5: Platelet-derived CD154 has an integral role in atherogenic plaque production.

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Acknowledgements

The authors thank A. H. Lazarus, H. Ni and V. Leytin for their helpful discussions and advice.

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Glossary

Megakaryocyte

A giant multinucleated cell of the bone marrow that gives rise to platelets.

Thrombocytopenia

Any disorder in which there is an abnormally low number of platelets (below 150,000 platelets per microlitre of blood). Thrombocytopenia is caused either by increased breakdown of platelets (in the blood, spleen or liver) or by low production of platelets.

Immune thrombocytopenia

An abnormal drop in platelet numbers caused by the presence of platelet-specific antibodies. Platelet production may be normal or impaired, as the disorder can also be caused by antibodies directed against megakaryocytes. The term includes autoimmune, alloimmune and certain drug-induced thrombocytopenias.

Toll-like receptors

A family of pattern recognition receptors that have essential roles in innate immunity. They are a class of single-membrane-spanning receptors that have the ability to recognize structurally conserved molecules from bacteria. Engagement of Toll-like receptors activates the immune response.

Tissue factor

The major cellular initiator of clot formation. It is essential for generating thrombin from the zymogen prothrombin.

Neutrophil extracellular traps

Networks of extracellular fibres, produced by neutrophils, that catch and help kill pathogens. The extracellular fibril matrix is composed of decondensed chromatin.

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Semple, J., Italiano, J. & Freedman, J. Platelets and the immune continuum. Nat Rev Immunol 11, 264–274 (2011). https://doi.org/10.1038/nri2956

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