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

• Published in: Blood advances Vol. 5; no. 5; pp. 1523 - 1534
• Main Authors: Courjon, Johan, Dufies, Océane, Robert, Alexandre, Bailly, Laurent, Torre, Cédric, Chirio, David, Contenti, Julie, Vitale, Sébastien, Loubatier, Céline, Doye, Anne, Pomares-Estran, Christelle, Gonfrier, Géraldine, Lotte, Romain, Munro, Patrick, Visvikis, Orane, Dellamonica, Jean, Giordanengo, Valérie, Carles, Michel, Yvan-Charvet, Laurent, Ivanov, Stoyan, Auberger, Patrick, Jacquel, Arnaud, Boyer, Laurent
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2021; American Society of Hematology
• Subjects: Biomarkers - blood; Case-Control Studies; Clinical Trials and Observations; COVID-19 - blood; COVID-19 - immunology; Humans; Inflammasomes - blood; Inflammasomes - metabolism; Middle Aged; Myeloid Cells - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; Prospective Studies; SARS-CoV-2 - immunology; SARS-CoV-2 - isolation & purification
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020003918

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. •Measurement of NLRP3 inflammasome activation in the blood of patients reveals an impaired immature neutrophil response in severe COVID-19.•Inflammasome signature analysis in circulating myeloid cells allows COVID-19 patients to be stratified and predicts evolution. [Display omitted]