Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity

Blood Advances - Tập 5 - Trang 1523-1534 - 2021
Johan Courjon1,2, Océane Dufies1, Alexandre Robert1,3, Laurent Bailly2,4, Cédric Torre1, David Chirio2, Julie Contenti2, Sébastien Vitale1,2, Céline Loubatier1, Anne Doye1, Christelle Pomares-Estran1,2, Géraldine Gonfrier2, Romain Lotte1,2, Patrick Munro1, Orane Visvikis1, Jean Dellamonica2, Valérie Giordanengo1,2, Michel Carles2, Laurent Yvan-Charvet1, Stoyan Ivanov1
1Université Côte d'Azur, Inserm, C3M, Nice, France
2Université Côte d'Azur, CHU Nice, Nice, France
3Service de Médecine Intensive Réanimation, Centre Hospitalier de Cannes, Cannes, France
4Public Health Department, University Hospital of Nice, Université Côte d’Azur, Nice, France

Tóm tắt

Abstract Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

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Blood Advances

Tập 5

1523-1534

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