PXD065321

PXD065321 is an original dataset announced via ProteomeXchange.

Title	Unraveling the immunosuppressive role of Elastase B produced by cystic fibrosis isolates of Pseudomonas aeruginosa in an organotypic 3-D lung epithelial cell model
Description	Pseudomonas aeruginosa chronically infects the lungs of people with cystic fibrosis (pwCF), where it produces a broad range of proteases that impact host immunity and inflammation. While some studies suggest these enzymes induce inflammation and may contribute to the excessive inflammatory response in pwCF, others indicate that they degrade cytokines and suppress the immune response. Here, we investigate the role of P. aeruginosa proteases in chronic CF lung inflammation by culturing clinical isolates under physiologically relevant conditions (synthetic CF sputum medium) and studying the inflammatory response in an organotypic 3-D lung cell culture model. Exposure to supernatants from isolates with proteolytic and elastolytic activity led to cytokine degradation and reduced cytokine release in the 3-D lung model. To identify the specific protease(s) responsible for the observed degradation effects, we performed a proteomics analysis on the supernatants of the P. aeruginosa CF isolates with and without proteolytic and elastolytic activity. Using functional annotation, 79 proteases were identified in the supernatants of the clinical isolates, with extracellular proteases among the most differentially expressed in the proteolytically active isolate group. The metalloprotease Elastase B (LasB) exhibited the highest level of differential expression. Therefore, we determined the specific contribution of LasB to the observed cytokine degradation by utilizing P. aeruginosa lasB knockout mutants. Compared to the lasB mutant, the wild-type strain significantly decreased inflammation by degrading key lung cytokines including MCP-1, IL-1β, GM-CSF and IL-8. While this study brings to light a key role for LasB, our findings demonstrate that immunomodulation by P. aeruginosa most likely involves the combined action of multiple proteases. This study provides a foundation for future research into protease-mediated immune evasion during chronic infection.
HostingRepository	PRIDE
AnnounceDate	2025-10-23
AnnouncementXML	Submission_2025-10-23_02:58:23.395.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Dufour
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Pseudomonas aeruginosa PAO1; NCBI TaxID: NEWT:208964;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-23 04:05:59	ID requested
⏵ 1	2025-10-23 02:58:23	announced

Dataset with its publication pending

submitter keyword: cystic fibrosis, proteomics, inflammation, Elastase B,Pseudomonas aeruginosa, bacterial proteases, virulence factors

Aurélie Crabbé
contact affiliation	Unraveling the immunosuppressive role of Elastase B produced by cystic fibrosis isolates of Pseudomonas aeruginosa in an organotypic 3-D lung epithelial cell model
contact email	aurelie.crabbe@ugent.be
lab head
Sara Dufour
contact affiliation	VIB-UGent
contact email	sara.dufour@vib-ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065321
     1. Label: PRIDE project
     2. Name: Unraveling the immunosuppressive role of Elastase B produced by cystic fibrosis isolates of Pseudomonas aeruginosa in an organotypic 3-D lung epithelial cell model