Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


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


Accumulating 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-alpha and IL-1beta 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-alpha and IL-1beta. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19.

Authors: Hottz ED, Martins-Gonçalves R, Palhinha L, Azevedo-Quintanilha IG, de Campos MM, Sacramento CQ, Temerozo JR, Soares VC, Dias SSG, Teixeira L, Castro IMS, Righy C, Souza TML, Kurtz P, Andrade B, Nakaya H, Monteiro RQ, Bozza FA, Bozza PT,
Journal: Blood Adv;2022Apr14. doi:10.1182/bloodadvances.2021006680
Year: 2022
PubMed: PMID: 35420680 (Go to PubMed)