PXD039805 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Brain Endothelial Cells Exposure to Malaria Parasites Links Type I Interferon Signalling to Antigen Presentation, Immunoproteasome Activation Endothelium Disruption, and Cellular Metabolism |
Description | Cerebral malaria (CM) lethality is attributable to brain edema induction but the cellular mechanisms involving brain microvascular endothelium in CM pathogenesis are unexplored. Activation of the STING-INFb-CXCL10 axis in brain endothelial cells (BECs) is a prominent component of the innate immune response in cerebral malaria (CM) development in mouse models. Using a T cell-reporter system, we show that Type 1 IFN signaling in BECs exposed to Plasmodium berghei-infected erythrocytes (PbA-IE), functionally enhances MHC Class-I antigen presentation through gamma-interferon independent immunoproteasome activation and impacted the proteome functionally related to vesicle trafficking, protein processing, and folding and antigen presentation. In vitro assays show that Type 1 IFN signaling and immunoproteasome activation are also involved in the dysfunction of the endothelial barrier through disturbing gene expression in the Wnt/ß-catenin signaling pathway. We demonstrate that IE exposure induces a substantial increase in BECs glucose uptake while glycolysis blockade abrogates INFb secretion impairing immunoproteasome activation, antigen presentation, and Wnt/ ß-catenin signaling. Metabolome analysis show that energy demand and production are markedly increased in BECs exposed to IE as revealed by enriched content in glucose and fatty acid catabolites. In accordance, glycolysis blockade in vivo delayed the clinical onset of CM in mice. Our results unveiled that Type 1 IFN signaling and subsequent immunoproteasome activation in BECs contribute to enhanced antigen presentation and the impairment of the endothelial barrier function. We also show that Type 1 IFN signaling and its downstream effects are licensed by dramatic increase in glucose uptake with an impact on energy metabolism pathways. This work raises the hypothesis that Type 1 IFN- immunoproteasome induction response in BECs contributes to CM pathology and fatality (1) by increasing antigen presentation to cytotoxic CD8+ T cells, which is a determinant of brain cytotoxic edema and (2) by promoting endothelial barrier dysfunction, that likely favors brain vasogenic edema. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_09:00:35.610.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Akos Vegvari |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-02-02 08:31:50 | ID requested | |
1 | 2023-03-13 08:30:32 | announced | |
⏵ 2 | 2023-11-14 09:00:36 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Cerebral malaria, Type I interferon, endotherial cells, Wnt/beta-catenin signaling |
Contact List
Akos Vegvari |
contact affiliation | Proteomics Biomedicum, Karolinska Institutet, Stockholm, Sweden |
contact email | akos.vegvari@ki.se |
lab head | |
Akos Vegvari |
contact affiliation | Karolinska Institutet |
contact email | akos.vegvari@ki.se |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039805
- Label: PRIDE project
- Name: Brain Endothelial Cells Exposure to Malaria Parasites Links Type I Interferon Signalling to Antigen Presentation, Immunoproteasome Activation Endothelium Disruption, and Cellular Metabolism