PXD044102-1

PXD044102 is an original dataset announced via ProteomeXchange.

Title	A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis to promote parasite chronicity
Description	The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of chronic intestinal helminth infection, we identify helminthic glutamate dehydrogenase (heGDH) as an essential factor for parasite chronicity by using antibody mediated neutralization or treatment with exogenous recombinant heGDH. Macrophages efficiently internalize heGDH and represent a major target of the enzyme in vivo. Combining RNA-seq, ChIP-seq, targeted lipidomics and inhibitor studies, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and further immune regulatory factors (IL-12 family cytokines, IDO1) by heGDH depended on the p300-mediated acetylation of histones. While the enzyme’s catalytic activity was dispensable for key immune regulatory functions, an N-terminal handle-like structure distinct from mammalian GDHs may confer interaction of heGDH with its targets (CD64, GPNMB), identified via proteomics. Thus, helminths employ a ubiquitous metabolic enzyme to epigenetically target macrophages and establish chronicity.
HostingRepository	PRIDE
AnnounceDate	2025-08-12
AnnouncementXML	Submission_2025-08-12_05:20:48.225.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ann-Christine König
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-26 05:57:51	ID requested
⏵ 1	2025-08-12 05:20:49	announced

Bohnacker S, Henkel FDR, Hartung F, Geerlof A, Riemer S, Prodjinotho UF, Salah EB, Mour, ã, o ASD, Bohn S, Teder T, Thomas D, Gurke R, Boeckel C, Ud-Dean M, K, ö, nig AC, Quaranta A, Alessandrini F, Lechner A, Spitzlberger B, Kabat AM, Pearce E, Haeggstr, ö, m JZ, Hauck SM, Wheelock CE, Jakobsson PJ, Sattler M, Voehringer D, Feige MJ, da Costa CP, Esser-von Bieren J, A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis. Sci Immunol, 9(102):eadl1467(2024) [pubmed]

10.1126/sciimmunol.adl1467;

submitter keyword: A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis to promote parasite chronicity

Julia Esser-von Bieren
contact affiliation	Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, 80802 Munich, Germany Department of Immunobiology, Université de Lausanne, 1066 Epalinges, Switzerland
contact email	julia.esser-vonbieren@unil.ch
lab head
Ann-Christine König
contact affiliation	HMGU Core Facility Proteomics
contact email	ann-christine.koenig@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD044102

PRIDE project URI

• PRIDE
  1. PXD044102
     1. Label: PRIDE project
     2. Name: A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis to promote parasite chronicity