PXD052925

PXD052925 is an original dataset announced via ProteomeXchange.

Title	Inhibition of tumour necrosis factor alpha by Etanercept attenuates Shiga toxin-induced brain pathology
Description	Infection with enterohemorrhagic E. coli (EHEC) causes severe changes in the brain leading to angiopathy, encephalopathy and microglial activation. In this study, we investigated the role of tumour necrosis factor alpha (TNF-α) for microglial activation and brain pathology using a preclinical mouse model of EHEC infection. LC–MS/MS proteomics of mice injected with a combination of Shiga toxin (Stx) and lipopolysaccharide (LPS) revealed extensive alterations of the brain proteome, in particular enrichment of pathways involved in complement activation and coagulation cascades. Inhibition of TNF-α by the drug Etanercept strongly mitigated these changes, particularly within the complement pathway, suggesting TNF-α-dependent vasodilation and endothelial injury. Analysis of microglial populations using a novel human-in-the-loop deep learning algorithm for the segmentation of microscopic imaging data indicated specific morphological changes, which were reduced to healthy condition after inhibition of TNF-α. Moreover, the Stx/LPS-mediated angiopathy was significantly attenuated by inhibition of TNF-α. Overall, our findings elucidate the critical role of TNF-α in EHEC-induced brain pathology and highlight a potential therapeutic target for mitigating neuroinflammation, microglial activation and injury associated with EHEC infection.
HostingRepository	PRIDE
AnnounceDate	2025-02-18
AnnouncementXML	Submission_2025-02-18_02:04:30.518.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bente Siebels
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-07 07:10:16	ID requested
⏵ 1	2025-02-18 02:04:31	announced

Christ R, Siemes D, Zhao S, Widera L, Spangenberg P, Lill J, Thiebes S, Bottek J, Borgards L, Pinho AG, Silva NA, Monteiro S, Jorch SK, Gunzer M, Siebels B, Voss H, Schl, ü, ter H, Shevchuk O, Chen J, Engel DR, Inhibition of tumour necrosis factor alpha by Etanercept attenuates Shiga toxin-induced brain pathology. J Neuroinflammation, 22(1):33(2025) [pubmed]

10.1186/s12974-025-03356-z;

submitter keyword: microglial activation, brain pathology, TNFα (tumour necrosis factor alpha), Etanercept,EHEC (enterohemorrhagic E. coli)

Prof. Dr.
contact affiliation	Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
contact email	danielrobert.engel@uni-due.de
lab head
Bente Siebels
contact affiliation	Section for Mass spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
contact email	b.siebels@uke.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/2025/02/PXD052925

PRIDE project URI

• PRIDE
  1. PXD052925
     1. Label: PRIDE project
     2. Name: Inhibition of tumour necrosis factor alpha by Etanercept attenuates Shiga toxin-induced brain pathology