PXD072930-1

PXD072930 is an original dataset announced via ProteomeXchange.

Title	Exosome-Mediated Bidirectional Immune Dysregulation in Tuberculosis: Proteomic Profiling Reveals Strain-Specific Strategies of Virulent H37Rv and Attenuated H37Ra
Description	Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis, with drug resistance and immune evasion complicating control efforts. Mtb subverts macrophage function to establish persistent infection, but the role of exosomes in immune regulation remains poorly understood. This study employed iTRAQ-based proteomics to dissect strain-specific immune modulation strategies of virulent H37Rv (RV) and attenuated H37Ra (RA) through macrophage and exosome profiling. We revealed distinct survival strategies of Mtb in Macrophages: RV maintained host cell viability and intracellular proliferation, while RA induced apoptosis. Human proteomic profiling identified significantly more upregulated host proteins in RA-infected macrophages than in RV-infected cells, with RA robustly activating antigen presentation pathways. Conversely, exosomes from infected macrophages exhibited overall protein downregulation, particularly for RV. Strikingly, of the top enriched pathways were upregulated intracellularly but downregulated in exosomes, indicating bidirectional immune dysregulation. Bacterial proteomics revealed that functional proteins were preferentially sorted into exosomes. RV-exosomes were enriched in dormancy regulators (e.g., DevS) and immunosuppressive effectors, while RA-exosomes carried immunogenic antigens leading to robust cytokines releasing such as THF-α,IL-1α and IL-6. Conclusively, Mtb exploits exosomes as "virulence vectors" to deliver RhoGDI and death signals (e.g., Caspse-9), paralyzing systemic immunity while optimizing intracellular survival. Virulence-specific cargo sorting informs novel diagnostics and therapies against TB.
HostingRepository	iProX
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-11_23:35:58.643.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lingna Lyu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-11 23:35:45	ID requested
⏵ 1	2026-01-11 23:35:59	announced

Dataset with its publication pending

submitter keyword: Exosomes, Immune Evasion, macrophage, Mycobacterium tuberculosis, Proteomics, Strain virulence

Lingna Lyu
contact affiliation	Beijing Youan Hospital, Capital Medical University
contact email	lvlingna003@163.com
lab head
Lingna Lyu
contact affiliation	Beijing Youan Hospital, Capital Medical University
contact email	lvlingna003@163.com
dataset submitter

iProX dataset URI