PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Bohnacker, S. ; Henkel, F. ; Hartung, F. ; Geerlof, A. ; Riemer, S. ; Prodjinotho, U.F.* ; Salah, E.B.* ; Mourao, A. ; Bohn, S. ; Teder, T.* ; Thomas, D.* ; Gurke, R.* ; Böckel, C. ; Ud-Dean, M. ; König, A.-C. ; Quaranta, A.* ; Alessandrini, F. ; Lechner, A. ; Spitzlberger, B. ; Kabat, A.M.* ; Pearce, E.J.* ; Haeggström, J.Z.* ; Hauck, S.M. ; Wheelock, C.E.* ; Jakobsson, P.J.* ; Sattler, M. ; Voehringer, D.* ; Feige, M.J.* ; da Costa, C.P.* ; Esser-von Bieren, J.

A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis.

Sci. Immunol. 9:eadl1467 (2024)
Publ. Version/Full Text DOI PMC
Free by Publisher
Open Access Green as soon as Postprint is submitted to ZB.
The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri (Hpb), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme's catalytic activity suppressed the synthesis of type 2-promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.
Impact Factor
Scopus SNIP
Altmetric
17.800
0.000
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Ccp4 Suite; Cells; Inflammation; Polarization; Activation; Expression; Phenotype; Proteome; Type-1; Focus
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2470-9468
e-ISSN 2470-9468
Journal Science immunology
Quellenangaben Volume: 9, Issue: 102, Pages: , Article Number: eadl1467 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
Institute of Structural Biology (STB)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)
POF-Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Research field(s) Allergy
Enabling and Novel Technologies
PSP Element(s) G-554600-001
G-505400-001
G-503000-001
G-503800-001
G-505700-001
A-630700-001
Grants Swedish Research Council
Swiss National Science Foundation
Helmholtz Young Investigator grant by the Helmholtz Initiative and Networking Fund
German Federal Ministry of Education and Research (BMBF)
German Research Foundation
DOI 10.1126/sciimmunol.adl1467
WOS ID 001372628200002
Scopus ID 85211750904
PubMed ID 39642243
Erfassungsdatum 2024-12-10
[➜Report correction]