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

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

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(+)CD16(dim) granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b(+)CD16(dim) 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(+)CD16(dim) 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.