PXD045819-1

PXD045819 is an original dataset announced via ProteomeXchange.

Title	Aspergillus fumigatus-derived gliotoxin impairs innate immune cell activation through modulating lipid mediator production in macrophages
Description	Gliotoxin (GT), a major secondary metabolite and virulence factor of Aspergillus fumigatus, suppresses innate immunity and supports the evasion of host immune responses. Recently, we revealed that GT blocks leukotriene (LT)B4 formation by directly inhibiting LTA4 hydrolase (LTA4H) in activated human neutrophils and monocytes. Here, we elucidated the impact of GT on LTB4 biosynthesis and the complex lipid mediator network in human M1- and M2-like monocyte-derived macrophage (MDM) subtypes and studied the respective consequences for innate immune cell functions. Notably, in resting MDMs, GT elicited prostaglandin and 12/15-lipoxygenase product formation, although less efficient than bacterial exotoxins. In activated MDM, LTB4 formation was effectively suppressed by GT, connected to impaired macrophage phagocytic activity, and detrimental consequences for neutrophil movement and migration. Conclusively, GT impairs functions of activated innate immune cells through suppression of LTB4 formation, while GT may prime the immune system by provoking prostaglandin formation and 12/15-lipoxygenase-derived LM.
HostingRepository	PRIDE
AnnounceDate	2024-11-13
AnnouncementXML	Submission_2024-11-13_15:07:23.146.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-29 09:14:42	ID requested
⏵ 1	2024-11-13 15:07:24	announced

10.1111/imm.13857;

G, ü, nther K, Nischang V, Cseresny, é, s Z, Kr, ü, ger T, Sheta D, Abboud Z, Heinekamp T, Werner M, Kniemeyer O, Beilhack A, Figge MT, Brakhage AA, Werz O, Jordan PM, Aspergillus fumigatus-derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages. Immunology, 173(4):748-767(2024) [pubmed]

submitter keyword: Aspergillus fumigatus, lipid mediators, macrophages,Gliotoxin, LC-MS/MS

Axel A. Brakhage
contact affiliation	Department for Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute Jena, Germany
contact email	axel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045819
     1. Label: PRIDE project
     2. Name: Aspergillus fumigatus-derived gliotoxin impairs innate immune cell activation through modulating lipid mediator production in macrophages