The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases

Abstract

Platelets are anucleate cells produced by megakaryocytes. In recent years, a robust body of literature supports the evolving role of platelets as key sentinel and effector cells in infectious diseases, especially critical in bridging hemostatic, inflammatory, and immune continuums. Upon intravascular pathogen invasion, platelets can directly sense viral, parasitic, and bacterial infections through pattern recognition receptors and integrin receptors or pathogen: immunoglobulin complexes through Fc and complement receptors—although our understanding of these interactions remains incomplete. Constantly scanning for areas of injury or inflammation as they circulate in the vasculature, platelets also indirectly respond to pathogen invasion through interactions with leukocytes and the endothelium. Following antigen recognition, platelets often become activated. Through a diverse repertoire of mechanisms, activated platelets can directly sequester or kill pathogens, or facilitate pathogen clearance by activating macrophages and neutrophils, promoting neutrophil extracellular traps (NETs) formation, forming platelet aggregates and microthrombi. At times, however, platelet activation may also be injurious to the host, exacerbating inflammation and promoting endothelial damage and thrombosis. There are many gaps in our understandings of the role of platelets in infectious diseases. However, with the emergence of advanced technologies, our knowledge is increasing. In the current review, we mainly discuss these evolving roles of platelets under four different infectious pathogen infections, of which are dengue, malaria, Esterichia coli (E. coli) and staphylococcus aureus S. aureus, highlighting the complex interplay of these processes with hemostatic and thrombotic pathways.

Immunologic Biomarkers, Morbidity and Mortality Among HIV Patients Hospitalized in a Tertiary Care Hospital in the Brazilian Amazon

“…Conversely, our multivariate analysis showed that, as the PDW values increased, the probability of death decreased. Thus, our data suggest the role of platelets as host defense effectors in agreement with these studies [38][39][40][41][42] .…”

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“…Similar to agonist-activation, the binding of pathogens can trigger granule cargo release [31] and liberation of "platelet microbial" proteins and peptides, including platelet factor (PF)-4, regulated on activation, normal T cell expressed and secreted (RANTES), and fibrinopeptide B. Platelets may also play an important role in the clearance of viral pathogens. Platelet interactions with leukocytes trigger recruitment and tissue infiltration necessary for pathogen clearance (reviewed in Guo [32]. In critically ill patients, The available clinical and pathological evidence, coupled with strong and mature data that supports a relationship between CFRNA, polyphosphate and factor XI activation, raises a logical scientific premise that requires investigation.…”

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“…Finally, during an E. coli infection, thromboinflammation is upregulated by simultaneous activation of FcγRIIA receptors and the αIIbβ3 integrin on platelets [ 25 ]. Bacterial killing of E. coli by platelets requires both FcγRIIA and platelet factor 4 (PF4) in order for destruction to occur [ 26 ]. Although the αIIbβ3 integrin is not directly involved in immune response against E. coli , it is a necessary component for the activation of platelet FcγRIIA and can lead to an upregulation of thromboinflammation.…”

“…Neutrophils in PNCs display a greater level of activation than those uncoupled from platelets, expressing more superoxide and phagocytosing more bacteria than their counterparts [ 31 ]. In fact, terms like “thromboinflammation” and “immunohemostasis” have gained traction in recent years in order to properly describe the interactive role of PNC’s in the immune response [ 26 ]. Upon activation via a variety of infection or inflammation mechanisms, platelets can change expression of their surface receptors to attach to other platelets, leukocytes, or extracellular pathogens, forming a complex that can help sequester and eliminate the pathogen [ 26 ].…”