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Series GSE85597 Query DataSets for GSE85597
Status Public on Jan 01, 2017
Title Extracellular Matrix Proteolysis by MT1-MMP is Associated with Influenza-Related Mortality
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The balance between protecting tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection using a combined genomic and proteomic approach. We followed the transcriptional dynamics and ECM- related responses in a mouse model of influenza virus infection, integrated with whole tissue imaging and functional assays. Our study identifies MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza virus infection. We show that selective inhibition of MT1-MMP-driven ECM proteolysis protects the tissue from infection-related structural and compositional damage. Inhibition of MT1-MMP did not significantly alter the immune response or cytokine expression, indicating its dominant role in ECM remodeling. We demonstrate that the available treatment for influenza virus (Tamiflu/ Oseltamivir) does not prevent lung ECM damage and is less effective than anti-MT1-MMP treatment in influenza virus and Streptococcus pneumoniae coinfection paradigms. Importantly, combination therapy of Tamiflu with anti-MT1-MMP shows a strong synergistic effect and results in complete recovery in mice. This study highlights the importance of tissue tolerance agents for surviving infectious diseases, and the potential of such host-pathogen therapy combination for respiratory infections.
Overall design Overall 8 samples were included, in duplicates, both infected and non-infected control cells were includeda. Both MT1-MMP positive and MT1-MMP negative were tested were non-infectdd, MT1-MMP negative cells served as controls.
Contributor(s) Frank DT, Altboum Z, Solomonov I, Udi Y, Jaitin DA, Klepfish M, David E, Zhuravlev A, Shaul HK, Winter DR, Viks IG, Mandelboim M, Ziv T, Amit I, Sagi I
Citation(s) 27736644
Submission date Aug 15, 2016
Last update date May 15, 2019
Contact name Ido Amit
Phone 972-8-9343338
Organization name Weizmann Institute of Science
Department Immunology
Street address 234 Herzl st.
City Rehovot
ZIP/Postal code 760001
Country Israel
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM2278995 1_Non_infectded_CD45_P_MMP_P
GSM2278996 2_Non_infectdde_CD45_P_MMP_P
GSM2278997 3_Non_infectded_CD45_MMP_P
BioProject PRJNA338920
SRA SRP082142

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Supplementary file Size Download File type/resource
GSE85597_20150515_homer.txt.gz 1.5 Mb (ftp)(http) TXT
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