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

dc.creatorHottz, Eugenio D.
dc.creatorGonçalves, Remy Martins
dc.creatorPalhinha, Lohanna
dc.creatorQuintanilha, Isaclaudia G. Azevedo
dc.creatorCampos, Mariana M. de
dc.creatorSacramento, Carolina Q.
dc.creatorTemerozo, Jairo R.
dc.creatorSoares, Vinicius Cardoso
dc.creatorGomes Dias, Suelen S.
dc.creatorTeixeira, Lívia
dc.creatorCastro, Ícaro
dc.creatorRighy, Cάssia
dc.creatorSouza, Thiago Moreno L.
dc.creatorKurtz, Pedro
dc.creatorAndrade, Bruno B.
dc.creatorNakaya, Helder I.
dc.creatorMonteiro, Robson Q.
dc.creatorBozza, Fernando A.
dc.creatorBozza, Patrícia T.
dc.date2022-05-09T15:47:15Z
dc.date2022-05-09T15:47:15Z
dc.date2022
dc.date.accessioned2023-09-26T22:56:59Z
dc.date.available2023-09-26T22:56:59Z
dc.identifierHOTTZ, Eugenio D. et al. Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19. Blood Advances, p. 1-54, 2022.
dc.identifier2473-9529
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/52589
dc.identifier10.1182/bloodadvances.2021006680
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8885115
dc.descriptionInova Fiocruz. Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
dc.descriptionAccumulating evidence into the pathogenesis of COVID-19 highlight 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-CoV2 infection. We used a combination of immunophenotyping, single cell analysis, functional assays and pharmacological approaches to gain insights on mechanisms. Critically ill COVID-19 patients 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 RNAseq analysis indicated enhanced fibrinogen receptor Mac-1 in monocytes from severe COVID-19 patients. Monocytes from severe COVID-19 patients displayed increased platelet binding and hyperresponsiveness to P-selectin and fibrinogen with respect to TFN-α and IL-1β secretion. Platelets were able to orchestrate monocyte responses driving 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, while TF signaling played major roles in amplifying inflammation by inducing proinflammatory cytokines, especially TNF-α and IL-1β. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society of Hematology
dc.rightsopen access
dc.subjectCOVID-19
dc.subjectTromboinflamação
dc.subjectCOVID-19
dc.subjectInteração plaqueta-monócito
dc.subject87 sinalização do fator tecidual
dc.subjectAmplificação inflamatória
dc.subjectThromboinflammation
dc.subjectCOVID-19
dc.subjectPlatelet-monocyte interaction
dc.subject87 tissue factor signaling
dc.subjectInflammatory amplification
dc.subjectTromboinflamación
dc.subjectCOVID-19
dc.subjectinteracción plaquetas-monocitos
dc.subject87 señalización del factor tisular
dc.subjectamplificación inflamatoria
dc.subjectThromboinflammation
dc.subjectInteraction plaquettes-monocytes
dc.subject87 signalisation du facteur tissulaire
dc.subjectamplification inflammatoire
dc.subjectCOVID-19
dc.subjectTromboplastina
dc.titlePlatelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19
dc.typeArticle


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