Platelets in Viral Infections – Brave Soldiers or Trojan Horses

Schrottmaier, Waltraud C.; Schmuckenschlager, Anna; Pirabe, Anita; Assinger, Alice

doi:10.3389/fimmu.2022.856713

Cited by 21 publications

(12 citation statements)

References 195 publications

(325 reference statements)

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“…The innate immune role of platelets in responding to infection is not restricted to bacteria as they also play an important role in responding to viruses (158)(159)(160)(161). The ability of pathogens to activate platelets has clinical implications.…”

Section: Pathogen-induced Platelet Activation: Clinical Implicationsmentioning

confidence: 99%

Sepsis – it is all about the platelets

Cox

2023

Front. Immunol.

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Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.

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Section: Pathogen-induced Platelet Activation: Clinical Implicationsmentioning

confidence: 99%

Sepsis – it is all about the platelets

Cox

2023

Front. Immunol.

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“…Response to viruses is among the ontology biological processes and signaling pathways enriched in MK L . Platelets have been involved in viral infection as reviewed previously ( 104 ). Among the genes significantly enriched, ifitm3 is encountered in the three mouse MK L studies and in circulating MKs during SARS-CoV-2 infection, as well as in platelets from infected patients ( 105 ).…”

Section: The Lung Environment Modulates Megakaryocytes and Platelet F...mentioning

confidence: 99%

Occurrence and role of lung megakaryocytes in infection and inflammation

2022

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Megakaryocytes (MKs) are large cells giving rise to platelets. It is well established that in adults, MKs develop from hematopoietic stem cells and reside in the bone marrow. MKs are also rare but normal constituents of the venous blood returning to the lungs, and MKs are found in the lung vasculature (MKcirc), suggesting that these cells are migrants from the bone marrow and get trapped in lung capillaries where the final steps of platelet production can occur. An unprecedented increase in the number of lung and circulating MKs was described in coronavirus disease 2019 (COVID-19) patients, suggesting that lung thrombopoiesis may be increased during lung infection and/or thromboinflammation. In addition to the population of platelet-producing intravascular MKs in the lung, a population of lung-resident megakaryocytes (MKL) has been identified and presents a specific immune signature compared to its bone marrow counterparts. Recent single-cell analysis and intravital imaging have helped us gain a better understanding of these populations in mouse and human. This review aims at summarizing the recent data on increased occurrence of lung MKs and discusses their origin, specificities, and potential role in homeostasis and inflammatory and infectious lung diseases. Here, we address remaining questions, controversies, and methodologic challenges for further studies of both MKcirc and MKL.

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“…Blood platelets play a crucial role in normal hemostasis as the initial responders to vascular injury and in thrombosis, particularly atherothrombosis (5). These effector cells also have important functions in inflammation and host defense (5)(6)(7)(8)(9). It is wellestablished that platelets, thrombosis and inflammation are intricately interconnected in numerous pathologies, including infectious diseases (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…These effector cells also have important functions in inflammation and host defense (5)(6)(7)(8)(9). It is wellestablished that platelets, thrombosis and inflammation are intricately interconnected in numerous pathologies, including infectious diseases (7)(8)(9). Platelet activation during severe COVID-19 is thought to contribute to the thromboembolic events and to worsen inflammatory response culminating in acute respiratory distress syndrome (ARDS).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant

Garcia,

Compagnon,

Ribes

et al. 2023

Front. Immunol.

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IntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.MethodsClinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.ResultsSevere Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.DiscussionAlthough SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.

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Platelets in Viral Infections – Brave Soldiers or Trojan Horses

Cited by 21 publications

References 195 publications

Sepsis – it is all about the platelets

Sepsis – it is all about the platelets

Occurrence and role of lung megakaryocytes in infection and inflammation

SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant

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