Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation

Abstract

Key Points In influenza-immune subjects, H1N1 influenza virus–containing immune complexes can activate platelets through FcγRIIA. H1N1 can also activate platelets through thrombin, independently of FcγRIIA, pointing to a role of coagulation in influenza infection.

Microvesicle Tissue Factor Activity and Interleukin-8 Levels are Associated with Mortality in Patients with Influenza A/H1N1 Infection

“…Other procoagulant markers and markers of inflammation or activation of coagulation were generally increased in patients with influenza but did not differ between survivors and non-survivors. Influenza virus can induce the expression of TF and the release of MVs, promoting a dysregulated pro-coagulant milieu (6). We posit that MV-TF activity in patients with influenza may not merely be a marker of severe infectious disease but may also contribute to adverse events such as vascular thrombosis, organ failure, and death.…”

“…Viruses, such as influenza, induce TF expression in monocytes and endothelial cells and activate the coagulation cascade, which can result in DIC (5). Influenza virus H1N1 also activates platelets and induces the release of MVs (6). However, there are no studies reporting levels of circulating TF-expressing MVs during the course of human influenza.…”

Nouvelle Cuisine: Platelets Served with Inflammation

“…The exposed PS, given its anionic properties, supports blood coagulation, although microparticles derived from platelets express modest levels of tissue factor (TF) and appear less procoagulant that do monocyte-derived microparticles, which express both PS and TF (113). In a recent study, Tersteeg et al (114) elegantly examined platelet activation Table I (8,125) Immune complexed bacterial components and epitopes of influenza viruses form PMPs via FcgRIIa (126,127) PMPs implicated in cell-cell communications via integrin, lactaderhin, and Del-1 (131, 132) PMP cargo consists of cytokines, chemokines, lipid mediators, enzymes, receptors, nucleic acids, autoantigens, transcription factors, mitochondria (103,(117)(118)(119)(128)(129)(130) under physiological flow and observed extremely long (up to 250 mm) membrane strands emerging from platelets, which is substantial considering their small size. These strands, called flow-induced protrusions, also expose PS, recruit neutrophils and monocytes (and not platelets), and appear to break off into PS + microparticles (114).…”

“…Platelets also participate in adaptive immunity through stimulation of FcgRIIA. Indeed, in immunized subjects, bacterial components and well-conserved epitopes expressed by influenza viruses are capable of forming immune complexes that activate FcgRIIA (126,127), leading to the formation of microparticles.…”

Platelets as immune-sensing cells

“…41 Several platelet surface receptors have been shown to trigger the formation of platelet microparticles such as GPVI during rheumatoid arthritis, 41 TLR4 signaling via lipopolysaccharide during sepsis, 42 and FcgRIIa, which may be targeted by immune complexes (of bacterial components or influenza viral epitopes). 43,44 The GPVI-and TLR4-mediated signals were also associated with increased IL-1 levels, illustrating their proinflammatory effects. Functionally, platelet microparticles can facilitate communication of platelets with other cells as they can carry a large variety of substances such as various cytokines or chemokines (eg, IL-1, RANTES), lipid mediators, enzymes, surface receptors like CD40L, autoantigens, transcription factors, and respiratory competent mitochondria, all of which can regulate immune functions.…”