PXD057656-1

PXD057656 is an original dataset announced via ProteomeXchange.

Title	Caspase-8’s non-apoptotic role is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.
Description	Excessive inflammation and cytokine release are hallmarks of severe COVID-19. Programmed cell death is known to drive inflammation, however, its relevance in the pathogenesis of severe COVID-19 is unclear. Using a combination of gene-targeted murine models and transcriptomic approaches we found that excessive cytokine release and inflammation are dependent on caspase-8. Loss of caspase-8 significantly reduced disease severity and viral loads in vivo. Importantly, this phenotype was not attributable to caspase-8’s role in apoptosis but was instead linked to a decrease in IL-1β levels and inflammation. Combined deficiency of pyroptosis, necroptosis, and apoptosis mediators (Caspase1/11/12/8/Ripk3-/-) provided no added benefit in ameliorating disease outcomes compared to C8/R3-/- mice. Transcriptional profiling of lung tissues in mice lacking caspase-8, and in compound mutants lacking caspase-8 and other additional caspases and mediators, confirmed that disease outcomes were not associated with transcription differences in cell death pathways, but rather to differences in pro-inflammatory responses. The expression of caspase-8 and FLIP was increased in the lungs of SARS-CoV-2 infected mice. Collectively, these findings identify a pivotal role for caspase-8 in driving the pathogenesis of severe SARS-CoV-2 infection through the modulation of pro-inflammatory cytokines but not through the induction of apoptosis.
HostingRepository	PRIDE
AnnounceDate	2025-09-20
AnnouncementXML	Submission_2025-09-19_18:59:32.964.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Tanzer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-08 01:48:36	ID requested
⏵ 1	2025-09-19 18:59:33	announced

Dataset with its publication pending

submitter keyword: SARS-CoV-2

Caspase-8

Inflammation

FLIP

COVID-19

Cytokines

Marcel Doerflinger
contact affiliation	Marcel Doerflinger, PhD Division of Infectious Diseases and Immune Defence The Walter and Eliza Hall Institute of Medical Research 1G Royal Parade, 3052 Parkville VIC, Australia
contact email	doerflinger.m@wehi.edu.au
lab head
Maria Tanzer
contact affiliation	Walter and Eliza Hall Institute
contact email	tanzer@wehi.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD057656

PRIDE project URI

• PRIDE
  1. PXD057656
     1. Label: PRIDE project
     2. Name: Caspase-8’s non-apoptotic role is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.