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

Courjon, Johan; Dufies, Océane; Robert, Alexandre; Bailly, Laurent; Torre, Cedric; Chirio, David; Contenti, Julie; Vitale, Sébastien; Loubatier, Céline; Doye, Anne; Pomares-Estran, C.; Gonfrier, Géraldine; Lotte, Romain; Munro, Patrick; Visvikis, Orane; Dellamonica, Jean; Giordanengo, Valérie; Carlès, Michel; Yvan‐Charvet, Laurent; Ivanov, Stoyan; Auberger, Patrick; Jacquel, Arnaud; Boyer, Laurent

doi:10.1182/bloodadvances.2020003918

Cited by 38 publications

(47 citation statements)

References 31 publications

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“…Even less frequently we were able to detect the ASC and GSDMD proteins which also indicates infrequent activation of inflammasome in critical COVID-19. Our results stay in accordance with recent findings that showed only small percentage of NLRP3 and AIM2 inflammasome activation in the circulating monocytes from COVID-19 patients 10,27 . Moreover, current data point at monocytes and macrophages as the major lung cell types showing activation of the inflammasome in COVID-19 9,10 .…”

Section: Discussionsupporting

confidence: 94%

Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients

Adamik

Ambrożek-Latecka

Dragan

et al. 2021

Preprint

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PurposeDevelopment of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins at the admission to the intensive care unit (ICU).Patients and methodsPlasma samples were obtained from 45 critically ill COVID-19 patients and from10 patients with severe traumatic brain injury (TBI) at the admission to the ICU. The concentration of IL-1α, IL-1β, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded.ResultsThe inflammasome-related biomarkers were in similar concentration in COVID-19 and TBI patients except for galectin-1 being lower in the former. None of the tested markers were related to the outcome, length of stay or development of secondary infections. Patients with SOFA score of >9 at admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients. Weak but significant correlations were observed between: IL-1α and platelets, IL-1β and platelets, ferritin and INR. Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. It was also significantly higher in patients with SOFA>9.ConclusionOur results indicate that the activation of the inflammasome in critically ill COVID-19 patients is a heterogenous process and is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

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Section: Discussionsupporting

confidence: 94%

Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients

Adamik

Ambrożek-Latecka

Dragan

et al. 2021

Preprint

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“…In particular, epigenetic loci are found in the AIM2 and MHC class I, C ( HLA-C ) genes [ 30 ]. Consistent with these findings, the levels of inflammasome-associated cytokines, including IL-1β and IL-18, were increased in the sera of patients with COVID-19 in the ICU [ 31 ]. Therefore, the NLRP3 inflammasome in myeloid cells has been proposed as a biomarker of COVID-19 severity [ 31 ].…”

Section: Inflammasome Complex and Sars-cov-2 Infection In Covid-19 Patientsmentioning

confidence: 63%

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

Cheon

Koo

2021

IJMS

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The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

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“…It has been proven that this viporin protein, indeed, allows the passage through the cell membrane of calcium ions that promote the activation of NLRP3 inflammasomes re-sulting in the production of IL-1β [ 143 , 144 , 145 , 146 ]. Therefore, the ionic movements begin the cytokine biosynthesis and potentially can support cytokine storms.…”

Section: Hyperinflammation and “Cytokine Storm” Uncontrolled Immune Responsesmentioning

confidence: 99%

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

Marcuzzi

Melloni

Zauli

et al. 2021

IJMS

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Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.

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

Cited by 38 publications

References 31 publications

Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients

Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

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