SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway.
iScience
; 24(4): 102295, 2021 Apr 23.
Article
in English
| MEDLINE | ID: covidwho-1122125
ABSTRACT
Macrophages promote an early host response to infection by releasing pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), TNF, and IL-6. The bioactivity of IL-1ß is classically dependent on NLRP3 inflammasome activation, which culminates in caspase-1 activation and pyroptosis. Recent studies suggest a role for NLRP3 inflammasome activation in lung inflammation and fibrosis in both COVID-19 and SARS, and there is evidence of NLRP3 involvement in HIV-1 disease. Here, we show that GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1, and HIV-1 trigger a TLR8-dependent pro-inflammatory cytokine response from human macrophages in the absence of pyroptosis, with GU-rich RNA from the SARS-CoV-2 spike protein triggering the greatest inflammatory response. Using genetic and pharmacological inhibition, we show that the induction of mature IL-1ß is through a non-classical pathway dependent on caspase-1, caspase-8, the NLRP3 inflammasome, potassium efflux, and autophagy while being independent of TRIF (TICAM1), vitamin D3, and pyroptosis.
Full text:
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Collection:
International databases
Database:
MEDLINE
Language:
English
Journal:
IScience
Year:
2021
Document Type:
Article
Affiliation country:
J.isci.2021.102295
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