PXD005169

PXD005169 is an original dataset announced via ProteomeXchange.

Title	Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and their Microparticles
Description	Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of frontline alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M. tb infection. Infection promoted a dramatic regulation of the macrophage proteome. Most notably, significant infection-dependent down-regulation (4-26 fold) of 11 lysosomal exoglycosidases e.g. β-galactosidase, β-hexosaminidases and α-/β-mannosidases was observed. Relative weak infection-driven transcriptional regulation of these exoglycosidases and a stronger augmentation of the extracellular hexosaminidase activity demonstrated that the lysosome-centric changes may originate predominantly from infection-induced secretion of the lysosomal content. The macrophages showed heterogeneous N-glycan profiles and displayed significant up-regulation of complex-type glycosylation and concomitant down-regulation of paucimannosylation upon infection. Complementary intact N-glycopeptide analysis supported a subcellular-specific manipulation of the glycosylation machinery and altered glycosylation patterns of lysosomal N-glycoproteins within infected macrophages. Interestingly, the corresponding macrophage-derived MPs displayed unique N-glycome and proteome signatures supporting a preferential packaging from plasma membranes. The MPs were devoid of infection-dependent N-glycosylation signatures, but interestingly displayed increased levels of the glyco-initiating oligosaccharyltransferase complex and associated α-glucosidases that correlated with increased formation, N-glycan precursor levels and N-glycan density of infected MPs. In conclusion, this system-wide study provides new insight into the host- and pathogen-driven N-glycoproteome manipulation of macrophages in TB.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:32:48.880.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD005169
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Propionamide; Deamidated; Dehydrated; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-17 03:49:35	ID requested
⏵ 1	2024-01-26 06:32:49	announced

10.6019/PXD005169;

10.3389/fimmu.2023.1258518;

Goodson H, Kawahara R, Chatterjee S, Goncalves G, Fehring J, Purcell AW, Croft NP, Thaysen-Andersen M, -glycan remodelling accompanies MHC-II immunopeptide presentation. Front Immunol, 14():1258518(2023) [pubmed]

curator keyword: Biomedical

submitter keyword: macrophage, proteomics,Mycobacterium tuberculosis, tuberculosis, glycoprofiling, microparticle, N-glycosylation, exoglycosidase, glycomics, glycoproteome, LC-MS/MS

Morten Thaysen-Andersen
contact affiliation	Department of Chemistry and Biomolecular Sciences Macquarie University Sydney, NSW 2109 Australia
contact email	morten.andersen@mq.edu.au
lab head
Ling Lee
contact affiliation	Macquarie University
contact email	lingyenlee@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005169
     1. Label: PRIDE project
     2. Name: Mycobacterium tuberculosis Infection Manipulates the Glycosylation Machinery and the N-Glycoproteome of Human Macrophages and their Microparticles