Inflammasome formation by neutrophils during COVID-19
Scandinavian Journal of Immunology
; 95(6), 2022.
Article
in English
| EMBASE | ID: covidwho-1968181
ABSTRACT
Type I interferons (IFN-I) induce the expression of several interferon-stimulated genes (ISGs), which provide antiviral capacity to host cells, including neutrophils. COVID-19 hyperinflammatory state involves an elevated neutrophilic response and can be aggravated by a heightened IFN-I response, associated with disease progression and severity. Numerous studies have proven significant inflammasome activation during SARS-CoV- 2 infection in patient circulating monocytes. However, despite the increased neutrophil counts seen in severe COVID-19 and the previously demonstrated capacity of these immune cells to form inflammasomes, little is known concerning the formation of these multiprotein complexes by neutrophils during acute COVID-19. Therefore, the aim of this study was to investigate neutrophil inflammasome formation and the possible role played by IFN-I. We found that COVID-19 isolated neutrophils exhibited a significant upregulation of ISGs and inflammasome genes in mature neutrophils, shown by RNA sequence and quantitative PCR, compared to healthy controls (HC). In vitro assays consisted of priming with lipopolysaccharide (LPS) or IFNa, and activating with nigericin, followed by measurements of IL-1β and caspase-1 levels. HC neutrophils responded to both priming signals, whereas COVID-19 neutrophils did not. After nigericin, both HC and COVID-19 neutrophils responded with a similar fold in IL-1β and caspase-1 levels. In conclusion, COVID-19 neutrophils showed upregulated inflammasome genes and increased inflammasome formation. Given the significant upregulation of ISGs and the demonstrated ability of IFN to prime neutrophils, a lack of response in COVID-19 neutrophils to priming signals suggests these cells were already primed, with IFN most likely playing a role.
alpha interferon; endogenous compound; inflammasome; interferon; interleukin 1beta; interleukin 1beta converting enzyme; lipopolysaccharide; multiprotein complex; nigericin; adult; conference abstract; controlled study; coronavirus disease 2019; enzyme activity; gene expression; human; human cell; immunocompetent cell; in vitro study; neutrophil; neutrophil count; protein function; real time polymerase chain reaction; RNA sequence; upregulation
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Scandinavian Journal of Immunology
Year:
2022
Document Type:
Article
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