PXD070363-1

PXD070363 is an original dataset announced via ProteomeXchange.

Title	Trained to respond: Signal-level modifications of endosomal TLRs
Description	Cells can modify their future behavior based on prior exposures, a phenomenon known as cellular adaptation. In innate immunity, such adaptive responses are critical for fine-tuning host defense, enabling trained immunity or tolerance. These states have been largely attributed to long-lasting epigenetic or metabolic reprogramming. Whether prior microbial encounters can rapidly lower receptor signaling thresholds to selectively enhance responsiveness of individual innate immune receptors remains unknown. Here, we identify a previously unrecognized, non-genetic form of cellular adaptation. We show that TLR4 activation by LPS, while inducing classical endotoxin tolerance, simultaneously primes macrophages for enhanced responses to subsequent activation of the RNA sensor TLR7. Because TLR4 and TLR7 use the same signaling machinery, this indicates that they are selectively reprogrammed in this process. TLR7 training requires type I interferons and is marked by a strong increase in Myddosome assemblies at endosomal membranes, without changes in TLR7 abundance or ligand uptake. These findings reveal that innate immune training can be rapidly encoded at the level of receptor-proximal signaling, linking microbial priming to enhanced nucleic acid immunity and potentially to TLR7-driven autoimmunity in genetically predisposed individuals.
HostingRepository	PRIDE
AnnounceDate	2025-12-16
AnnouncementXML	Submission_2025-12-16_14:38:06.013.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-05 09:14:23	ID requested
⏵ 1	2025-12-16 14:38:06	announced

Dataset with its publication pending

submitter keyword: None

Olivia Majer
contact affiliation	Max Planck Institute for Infection Biology Charitéplatz 1 D-10117 Berlin Germany
contact email	majer@mpiib-berlin.mpg.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.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/2025/12/PXD070363

PRIDE project URI

• PRIDE
  1. PXD070363
     1. Label: PRIDE project
     2. Name: Trained to respond: Signal-level modifications of endosomal TLRs