Details

Autor(en) / Beteiligte

• Hottz, Eugenio D.
• Martins-Gonçalves, Remy
• Palhinha, Lohanna
• Azevedo-Quintanilha, Isaclaudia G.
• de Campos, Mariana M.
• Sacramento, Carolina Q.
• Temerozo, Jairo R.
• Soares, Vinicius Cardoso
• Dias, Suelen S. Gomes
• Teixeira, Lívia
• Castro, Ícaro
• Righy, Cassia
• Souza, Thiago Moreno L.
• Kurtz, Pedro
• Andrade, Bruno B.
• Nakaya, Helder I.
• Monteiro, Robson Q.
• Bozza, Fernando A.
• Bozza, Patrícia T.

Titel

Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19

Ist Teil von

• Blood advances, 2022-09, Vol.6 (17), p.5085-5099

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Accumulating evidence into the pathogenesis of COVID-19 highlights a hypercoagulability state with high risk of life-threatening thromboembolic complications. However, the mechanisms of hypercoagulability and their link to hyperinflammation remain poorly understood. Here, we investigate functions and mechanisms of platelet activation and platelet-monocyte interactions in inflammatory amplification during SARS-CoV-2 infection. We used a combination of immunophenotyping, single-cell analysis, functional assays, and pharmacological approaches to gain insights on mechanisms. Critically ill patients with COVID-19 exhibited increased platelet-monocyte aggregates formation. We identified a subset of inflammatory monocytes presenting high CD16 and low HLA-DR expression as the subset mainly interacting with platelets during severe COVID-19. Single-cell RNA-sequencing analysis indicated enhanced fibrinogen receptor Mac-1 in monocytes from patients with severe COVID-19. Monocytes from patients with severe COVID-19 displayed increased platelet binding and hyperresponsiveness to P-selectin and fibrinogen with respect to tumor necrosis factor-α and interleukin-1β secretion. Platelets were able to orchestrate monocyte responses driving tissue factor (TF) expression, inflammatory activation, and inflammatory cytokines secretion in SARS-CoV-2 infection. Platelet-monocyte interactions ex vivo and in SARS-CoV-2 infection model in vitro reciprocally activated monocytes and platelets, inducing the heightened secretion of a wide panel of inflammatory mediators. We identified platelet adhesion as a primary signaling mechanism inducing mediator secretion and TF expression, whereas TF signaling played major roles in amplifying inflammation by inducing proinflammatory cytokines, especially tumor necrosis factor-α and interleukin-1β. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19. •Platelet-monocyte interaction engages a reciprocal activation loop that feeds thromboinflammation in COVID-19.•Platelet adhesion is a primary signaling mechanism for monocyte activation that is amplified by tissue factor-dependent signaling. [Display omitted]