Dataset Information

SERUM DATA FILES EMI TB PROTEOMICS

ABSTRACT: Five complete TMT10plex labellings including active TB patients and infected and uninfected contacts

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Monica Carrera

PROVIDER: MSV000083645 | MassIVE | Mon Apr 01 05:57:00 BST 2019

REPOSITORIES: MassIVE

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection.

Mateos Jesús J Estévez Olivia O González-Fernández África Á Anibarro Luis L Pallarés Ángeles Á Reljic Rajko R Mussá Tufária T Gomes-Maueia Cremildo C Nguilichane Artur A Gallardo José M JM Medina Isabel I Carrera Mónica M

Scientific reports 20200302 1

Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were anal ...[more]

PMID: 32123229

Similar Datasets

Project description:Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact on human and animal health worldwide. Mycobacterial life cycle is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals when compared to uninfected controls are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls but protein levels increased as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggested that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recover to limit pathogen multiplication and promote survival that also facilitates pathogen transmission.

Project description:Tuberculosis (TB) is an ancient infectious disease that remains one of the major health threats in humans worldwide. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These gene signature analyses were employed for pathognomonic associations, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed, and functional gene clusters of immunoregulatory interactions provide detailed insights into the dysregulation of critical immune processes in TB. Transcriptomics thus (i) provides a robust system for identification and validation of biosignatures for TB diagnosis and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis. A total of 46 sputum smear and chest x-ray positive TB patients (TB), 25 latently infected healthy donors (LTBI, TB case contacts with Mantoux test induration >= 10mm) and 37 uninfected donors (NID, Mantoux test induration = 0mm) were included from a cohort in The Gambia. All subjects were HIV– and samples from TB patients were taken prior to chemotherapy. Whole blood RNA was extracted using the PAXgene Blood RNA Kit (PreAnalytix) and labeled with Agilents Fluorescent Linear Amplification Kit. Quantity and labeling efficiency were verified before hybridization of the samples to whole-genome 4×44k human expression arrays and scanned at 5 μm using an Agilent scanner.