Dissecting Platelet’s Role in Viral Infection: A Double-Edged Effector of the Immune System (original) (raw)
Related papers
Platelets in immune Response to virus and immunopathology of viral infections
Platelets are essential effector cells in hemostasis. Aside from their role in coagulation, platelets are now recognized as major inflammatory cells with key roles in the innate and adaptive arms of the immune system. Activated platelets have key thromboinflammatory functions linking coagulation to immune responses in various infections, including in response to virus. Recent studies have revealed that platelets exhibit several pattern recognition receptors (PRR) including those from the toll-like receptor, NOD-like receptor, and C-type lectin receptor family and are first-line sentinels in detecting and responding to pathogens in the vasculature. Here, we review the main mechanisms of platelets interaction with viruses, including their ability to sustain viral infection and replication, their expression of specialized PRR, and activation of thromboinflammatory responses against viruses. Finally, we discuss the role of platelet-derived mediators and platelet interaction with vascular and immune cells in protective and pathophysiologic responses to dengue, influenza, and human immunodeficiency virus 1 infections.
Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword
International Journal of Molecular Sciences, 2021
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 pl...
Biology
Platelets have long been recognized for their role in maintaining the balance between hemostasis and thrombosis. While their contributions to blood clotting have been well established, it has been increasingly evident that their roles extend to both innate and adaptive immune functions during infection and inflammation. In this comprehensive review, we describe the various ways in which platelets interact with different microbes and elicit immune responses either directly, or through modulation of leukocyte behaviors.
Evidence of Toll-like receptor molecules on human platelets
Immunology and Cell Biology, 2005
Platelets are primarily involved in thrombosis and haemostasis, and they have recently been shown to have a role in innate immunity and in inflammation. We have determined the markers of innate immunity that are expressed by platelets, specifically the Toll-like receptors (TLR), originating from mixes of platelet concentrates (MPC, n = 5) between day zero and day five after blood collection. The surface membrane and intracellular expression of TLR were measured, both after and without permeabilization, using flow cytometry. We observed weak expression of TLR2, TLR4 and TLR9 on the surface of CD41 + platelets. The expression levels of TLR4 were high (59 ± 2.2%). Moreover, there was a significant expression of TLR2 (47.5 ± 4.8%), TLR4 (78.8 ± 1.3%) and TLR9 (34.2 ± 7.5%) in the cytoplasm of CD41 + platelets. The expression of the three receptors did not change significantly during the course of the 5 day observation period. The percentage of TLR expression is significantly modulated between activated versus non-activated platelets, both after and without permeabilization ( P < 0.01). Study of the expression of TLR could increase our knowledge of the level of platelet participation during an immune reaction and inflammation. In the same way as the platelet ligand/receptor pair CD40L/CD40 is, the TLR are expressed by platelets, and could serve as a link between innate and adaptive immunity.
Innate immune receptors in platelets and platelet‐leukocyte interactions
Journal of Leukocyte Biology, 2020
Platelets are chief cells in hemostasis. Apart from their hemostatic roles, platelets are major inflammatory effector cells that can influence both innate and adaptive immune responses. Activated platelets have thromboinflammatory functions linking hemostatic and immune responses in several physiological and pathological conditions. Among many ways in which platelets exert these functions, platelet expression of pattern recognition receptors (PRRs), including TLR, Nod-like receptor, and C-type lectin receptor families, plays major roles in sensing and responding to pathogen-associated or damage-associated molecular patterns (PAMPs and DAMPs, respectively). In this review, an increasing body of evidence is compiled showing the participation of platelet innate immune receptors, including PRRs, in infectious diseases, sterile inflammation, and cancer. How platelet recognition of endogenous DAMPs participates in sterile inflammatory diseases and thrombosis is discussed. In addition, platelet recognition of both PAMPs and DAMPs initiates platelet-mediated inflammation and vascular thrombosis in infectious diseases, including viral, bacterial, and parasite infections. The study also focuses on the involvement of innate immune receptors in platelet activation during cancer, and their contribution to tumor microenvironment development and metastasis. Finally, how innate immune receptors participate in platelet communication with leukocytes, modulating leukocyte-mediated inflammation and immune functions, is highlighted. These cell communication processes, including platelet-induced release of neutrophil extracellular traps, platelet Ag presentation to T-cells and platelet modulation of monocyte cytokine secretion are discussed in the context of infectious and sterile diseases of major concern in human health, including cardiovascular diseases, dengue, HIV infection, sepsis, and cancer.
Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries
Advances in Hematology, 2012
Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.
The prowess of platelets in immunity and inflammation
Thrombosis and Haemostasis
SummaryPlatelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease....
Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation
Journal of Thrombosis and Haemostasis, 2011
It has become clear that platelets are not simply cell fragments that plug the leak in a damaged blood vessel; they are, in fact, also key components in the innate immune system, which is supported by the presence of Toll-like receptors (TLRs) on platelets. As the cells that respond first to a site of injury, they are well placed to direct the immune response to deal with any resulting exposure to pathogens. The response is triggered by bacteria binding to platelets, which usually triggers platelet activation and the secretion of antimicrobial peptides. The main platelet receptors that mediate these interactions are glycoprotein (GP)IIb-IIIa, GPIba, FccRIIa, complement receptors, and TLRs. This process may involve direct interactions between bacterial proteins and the receptors, or can be mediated by plasma proteins such as fibrinogen, von Willebrand factor, complement, and IgG. Here, we review the variety of interactions between platelets and bacteria, and look at the potential for inhibiting these interactions in diseases such as infective endocarditis and sepsis.
Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation
International Journal of Molecular Sciences, 2022
There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbβ3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet–neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet–monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.
Platelet Function in Viral Immunity and SARS-CoV-2 Infection
Seminars in Thrombosis and Hemostasis
Platelets, as nonnucleated blood components, are classically recognized for their pivotal role in hemostasis. In recent years, however, accumulating evidence points to a nonhemostatic role for platelets, as active participants in the inflammatory and immune responses to microbial organisms in infectious diseases. This stems from the ability of activated platelets to secrete a plethora of immunomodulatory cytokines and chemokines, as well as directly interplaying with viral receptors. While much attention has been given to the role of the cytokine storm in the severity of the coronavirus disease 2019 (COVID-19), less is known about the contribution of platelets to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we give a brief overview on the platelet contribution to antiviral immunity and response during SARS-CoV-2 infection.