Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity
Johan Courjon, Océane Dufies, Alexandre Robert, Laurent Bailly, Cédric Torre, David Chirio, Julie Contenti, Sébastien Vitale, Céline Loubatier, Anne Doye, Christelle Pomares-Estran, Géraldine Gonfrier, Romain Lotte, Patrick Munro, Orane Visvikis, Jean Dellamonica, Valérie Giordanengo, Michel Carles, Laurent Yvan-Charvet, Stoyan Ivanov, Patrick Auberger, Arnaud Jacquel, Laurent Boyer, Johan Courjon, Océane Dufies, Alexandre Robert, Laurent Bailly, Cédric Torre, David Chirio, Julie Contenti, Sébastien Vitale, Céline Loubatier, Anne Doye, Christelle Pomares-Estran, Géraldine Gonfrier, Romain Lotte, Patrick Munro, Orane Visvikis, Jean Dellamonica, Valérie Giordanengo, Michel Carles, Laurent Yvan-Charvet, Stoyan Ivanov, Patrick Auberger, Arnaud Jacquel, Laurent Boyer
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.
Conflict of interest statement
Conflict-of-interest disclosure: The authors declare no competing financial interests.
© 2021 by The American Society of Hematology.
Figures
References
- Li Q, Guan X, Wu P, et al. . Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199-1207.
- Chan JF, Yuan S, Kok KH, et al. . A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514-523.
- Jamilloux Y, Henry T, Belot A, et al. . Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev. 2020;19(7):102567.
- Vabret N, Britton GJ, Gruber C, et al. ; Sinai Immunology Review Project . Immunology of COVID-19: current state of the science. Immunity. 2020;52(6):910-941.
- Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013-1022.
- Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol. 2015;16(4):343-353.
- Medzhitov R. Approaching the asymptote: 20 years later. Immunity. 2009;30(6):766-775.
- Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev. 2009;227(1):75-86.
- Chow KT, Gale M Jr., Loo YM. RIG-I and other RNA sensors in antiviral immunity. Annu Rev Immunol. 2018;36:667-694.
- Huang C, Wang Y, Li X, et al. . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
- Wen W, Su W, Tang H, et al. . Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing [published correction appears in Cell Discov. 2020;6:41]. Cell Discov. 2020;6:31.
- Conti P, Ronconi G, Caraffa A, et al. . Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):327-331.
- Vabret N, Samstein R, Fernandez N, Merad M; Sinai Immunology Review Project; Trainees; Faculty . Advancing scientific knowledge in times of pandemics. Nat Rev Immunol. 2020;20(6):338.
- Chen IY, Moriyama M, Chang MF, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019;10:50.
- Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages [published corrections appear in Nat Rev Immunol. 2020;20(7):448]. Nat Rev Immunol. 2020;20(6):355-362.
- Deftereos SG, Siasos G, Giannopoulos G, et al. . The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): rationale and study design. Hellenic J Cardiol. 2020;61(1):42-45.
- Parisi V, Leosco D. Precision medicine in COVID-19: IL-1β a potential target. JACC Basic Transl Sci. 2020;5(5):543-544.
- Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacol Res. 2020;158:104901.
- Rodrigues TS, de Sá KSG, Ishimoto AY, et al. . Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med. 2021;218(3):e20201707.
- Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, et al. . SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes. . Accessed 10 January 2021.
- World Health Organization (WHO) . Clinical Management of COVID-19: Interim Guidance. Geneva, Switzerland: WHO; 2020.
- Frat JP, Thille AW, Mercat A, et al. ; REVA Network . High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196.
- Martínez-García JJ, Martínez-Banaclocha H, Angosto-Bazarra D, et al. . P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis. Nat Commun. 2019;10(1):2711.
- Zhao Y, Qin L, Zhang P, et al. . Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease. JCI Insight. 2020;5(13):e139834.
- Groslambert M, Py BF. Spotlight on the NLRP3 inflammasome pathway. J Inflamm Res. 2018;11:359-374.
- Grieshaber-Bouyer R, Nigrovic PA. Neutrophil heterogeneity as therapeutic opportunity in immune-mediated disease. Front Immunol. 2019;10:346.
- Cavalli G, De Luca G, Campochiaro C, et al. . Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325-e331.
- Pillay J, Ramakers BP, Kamp VM, et al. . Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010;88(1):211-220.
- Silvin A, Chapuis N, Dunsmore G, et al. . Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020;182(6):1401-1418.e18.
- Schulte-Schrepping J, Reusch N, Paclik D, et al. ; Deutsche COVID-19 OMICS Initiative (DeCOI) . Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell. 2020;182(6):1419-1440.e23.
- Vitte J, Diallo AB, Boumaza A, et al. . A granulocytic signature identifies COVID-19 and its severity. J Infect Dis. 2020;222(12):1985-1996.
- Immunological Genome Project . ImmGen at 15. Nat Immunol. 2020;21(7):700-703.
- Wilk AJ, Rustagi A, Zhao NQ, et al. . A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020;26(7):1070-1076.
Source: PubMed