PXD069678-1

PXD069678 is an original dataset announced via ProteomeXchange.

Title	Incoming poxvirus dsDNA genomes differentially activate AIM2 or NLRP3 inflammasomes in human cells
Description	The innate immune system recognizes cytosolic DNA as evidence of infection, although detailed analysis is mostly limited to mice and cell lines. To investigate inflammasome responses in human primary cells, we used the inflammasome reporter caspase-1CARD-EGFP (C1C-EGFP) encoded in engineered viruses. We found that released genomes of the model poxvirus vaccinia virus (VACV) and monkeypox virus (MPXV) trigger robust inflammasome assembly in human primary cells. To determine the involved inflammasome sensors, we generated nanobodies against AIM2. Three of them inhibit AIM2 inflammasome assembly by blocking the polymerization of the AIM2 PYD, most potently as bivalent nanobodies. Utilizing VACV expressing bivalent AIM2 nanobodies, we show that inflammasomes in primary human macrophages and keratinocytes are nucleated by AIM2, while CD14+ monocytes assemble NLRP3 inflammasomes. This resolves the discrepancy between the previously reported activation of AIM2 inflammasomes in mice and NLRP3 inflammasomes in humans and provides the first evidence of cell-type-specific regulation of DNA-triggered inflammasome activation. The newly developed AIM2-specific nanobodies offer a precise tool to dissect and potentially target AIM2 inflammasome assembly in other disease contexts.
HostingRepository	PRIDE
AnnounceDate	2026-01-22
AnnouncementXML	Submission_2026-01-22_04:14:09.235.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tabea Klein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-20 11:46:37	ID requested
⏵ 1	2026-01-22 04:14:09	announced

10.1038/S44318-025-00690-Z;

submitter keyword: None

Florian Schmidt
contact affiliation	Institute for Innate Immunity, University Bonn, Germany
contact email	florian.schmidt@uni-bonn.de
lab head
Tabea Klein
contact affiliation	Institute for Innate Immunity, University Bonn
contact email	tabea.klein@ukbonn.de
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/2026/01/PXD069678

PRIDE project URI

• PRIDE
  1. PXD069678
     1. Label: PRIDE project
     2. Name: Incoming poxvirus dsDNA genomes differentially activate AIM2 or NLRP3 inflammasomes in human cells