PXD057300

PXD057300 is an original dataset announced via ProteomeXchange.

Title	PTP1B Deficiency in Myeloid Cells Increases Susceptibility to Candida albicans Infection by Modulating Anti-fungal Immunity
Description	Invasive candidiasis is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Understanding how the immune response towards Candida albicans is mounted and controlled is fundamental to developing new therapeutic strategies. Protein tyrosine phosphatase 1B (PTP1B) is a key phosphatase regulating various immunoreceptor signalling cascades including inflammatory and metabolic responses and a pharmaceutical target. This study uncovers the importance of PTP1B in driving protective antifungal immune cell responses post-infection. Following systemic C. albicans infection, mice lacking PTP1B in myeloid cells (LysM PTP1B-/-) were significantly more susceptible to infection, with lower survival rates, greater body weight loss and higher fungal burdens in brain, kidney, and liver. LysM PTP1B-/- infected mice exhibited increased expression of organ inflammatory cytokines TNF, IL-10, IL-6 and IL-1β and increased kidney tubular inflammation, 1- and 3-days post-infection. Kidneys from infected LysM PTP1B-/- mice also demonstrated significantly increased chemokine expression and leukocyte infiltration, collectively promoting immunopathology. PTP1B-/- neutrophils infiltrating into kidneys were, however, less mature and in vitro produced less ROS. Bone marrow-derived macrophages from LysM PTP1B-/- mice, through proteomic analysis, show enhancement of immune response and type I interferon signalling pathways, and they were less able to phagocytose and kill C. albicans relating to changes in their metabolism and viability when fighting infection. The decrease in phagocytosis and viability in PTP1B-/- macrophages following infection translated to human macrophages treated with a pharmacological PTP1B inhibitor. Our data provides new insights connecting the critical role of myeloid cell PTP1B in regulating immune defence against C. albicans through modulating levels of inflammatory cytokines, neutrophil clearance mechanisms and macrophage functional and metabolic responses, implying that boosting specific PTP1B-dependent signalling pathways could have therapeutic implications for combatting systemic fungal infection.
HostingRepository	PRIDE
AnnounceDate	2025-08-28
AnnouncementXML	Submission_2025-08-28_10:00:41.667.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alan Score
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Candida albicans (Yeast); NCBI TaxID: 5476;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-29 10:04:44	ID requested
⏵ 1	2025-08-28 10:00:42	announced

10.1128/MBIO.01516-25;

submitter keyword: PTP1B, fungal infection,Myeloid cell

J Simon C Arthur
contact affiliation	University of Dundee Cell Signalling and Immunology
contact email	jscarthur@dundee.ac.uk
lab head
Alan Score
contact affiliation	University of Dundee
contact email	a.j.score@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057300
     1. Label: PRIDE project
     2. Name: PTP1B Deficiency in Myeloid Cells Increases Susceptibility to Candida albicans Infection by Modulating Anti-fungal Immunity