PXD029017-1

PXD029017 is an original dataset announced via ProteomeXchange.

Title	Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis infected macrophages
Description	Necrotic cell death represents a major pathogenic mechanism of Mycobacterium tuberculosis (Mtb) infection. It is increasingly evident that Mtb induces several types of regulated necrosis but how these are interconnected and linked to the release of pro-inflammatory cytokines remains unknown. Exploiting a clinical cohort of tuberculosis patients, we show here that the number and size of necrotic lesions correlates with IL-1β plasma levels as a strong indicator of inflammasome activation. Our mechanistic studies reveal that Mtb triggers mitochondrial permeability transition (mPT) and subsequently extensive macrophage necrosis which requires activation of the NLRP3 inflammasome. NLRP3 driven mitochondrial damage is dependent on proteolytic activation of the pore forming effector protein gasdermin D (GSDMD) which links two distinct cell death machineries. Intriguingly, GSDMD, but not the membranolytic mycobacterial ESX-1 secretion system is dispensable for IL-1β secretion from Mtb-infected macrophages. Thus, our study dissects a novel mechanism of pathogen induced regulated necrosis by identifying mitochondria as central regulatory hubs capable of delineating cytokine secretion and lytic cell death.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_00:33:24.374.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-08 07:08:06	ID requested
⏵ 1	2022-02-17 00:33:26	announced
2	2024-10-22 05:32:38	announced	2024-10-22: Updated project metadata.

Theobald SJ, Gr, ä, b J, Fritsch M, Su, á, rez I, Eisfeld HS, Winter S, Koch M, H, ö, lscher C, Pasparakis M, Kashkar H, Rybniker J, secretion in Mycobacterium tuberculosis-infected macrophages. Cell Death Discov, 7(1):327(2021) [pubmed]

submitter keyword: Mycobacterium tuberculosis

Gasdermin D

Interleukin-1β

Cell death

ESX-1

Mitochondria

NLRP3

inflammasome

Jan Rybniker
contact affiliation	Department I of Internal Medicine, Cologne, Germany
contact email	Jan.rybniker@uk-koeln.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.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/2022/02/PXD029017

PRIDE project URI

• PRIDE
  1. PXD029017
     1. Label: PRIDE project
     2. Name: Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis infected macrophages