PXD004871

PXD004871 is an original dataset announced via ProteomeXchange.

Title	Dysregulated Proteolysis of Extracellular Matrix Proteins Regulates Influenza and Pneumonia Co-infection Associated Mortality
Description	The balance between tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extra cellular matrix (ECM)-remodeling events in the lung during influenza infection. Using an unbiased genomic and proteomic approach we follow the dynamics of gene and ECM responses in an influenza-infected mouse model, integrated with whole tissue as well as ECM imaging and functional assays. Our study identifies membrane type 1 matrix metalloproteinase (MT1-MMP) as a major host-regulated ECM remodeling collagenase in influenza infection. We show that inhibition of MT1-MMP-driven proteolytic activity protected tissue structural and compositional features. We demonstrate that available influenza treatment (Oseltamivir) is ineffective in preventing the lung ECM damage and is therefore less effective than anti-MT1-MMP treatment in influenza and Streptococcus pneumoniae co-infections. Importantly, the combination between the two treatments resulted in 100% survival. This study highlights the importance of ECM protection for survival during infectious diseases, and paves the way for combined host-pathogen theraphy to fight emerging pathogens.
HostingRepository	PRIDE
AnnounceDate	2019-11-19
AnnouncementXML	Submission_2019-11-19_12:26:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-19 02:06:26	ID requested
⏵ 1	2019-11-19 12:26:31	announced

Talmi-Frank D, Altboum Z, Solomonov I, Udi Y, Jaitin DA, Klepfish M, David E, Zhuravlev A, Keren-Shaul H, Winter DR, Gat-Viks I, Mandelboim M, Ziv T, Amit I, Sagi I, Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality. Cell Host Microbe, 20(4):458-470(2016) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Pneumonia, Influenza, Extracellular Matrix Proteins

Irit Sagi
contact affiliation	Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
contact email	Irit.Sagi@weizmann.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@tx.technion.ac.il
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/2019/11/PXD004871

PRIDE project URI

• PRIDE
  1. PXD004871
     1. Label: PRIDE project
     2. Name: Dysregulated Proteolysis of Extracellular Matrix Proteins Regulates Influenza and Pneumonia Co-infection Associated Mortality