tetano
Editor, Senior Moderator
Cell Host Microbe. 2016 Oct 12;20(4):458-470. doi: 10.1016/j.chom.2016.09.005.
[h=1]Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality.[/h] Talmi-Frank D[SUP]1[/SUP], Altboum Z[SUP]2[/SUP], Solomonov I[SUP]3[/SUP], Udi Y[SUP]3[/SUP], Jaitin DA[SUP]2[/SUP], Klepfish M[SUP]3[/SUP], David E[SUP]2[/SUP], Zhuravlev A[SUP]3[/SUP], Keren-Shaul H[SUP]2[/SUP], Winter DR[SUP]2[/SUP], Gat-Viks I[SUP]4[/SUP], Mandelboim M[SUP]5[/SUP], Ziv T[SUP]6[/SUP], Amit I[SUP]7[/SUP], Sagi I[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage. MT1-MMP inhibition did not significantly alter the immune response or cytokine expression. The available flu therapeutic Oseltamivir did not prevent lung ECM damage and was less effective than anti-MT1-MMP in influenza virus Streptococcus pneumoniae coinfection paradigms. Combination therapy of Oseltamivir with anti-MT1-MMP showed a strong synergistic effect and resulted in complete recovery of infected mice. This study highlights the importance of tissue resilience in surviving infection and the potential of such host-pathogen therapy combinations for respiratory infections.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] ECM remodeling; Influenza virus; MT1-MMP; host-pathogen gene regulation; immune genomics; matrix metalloproteinase inhibitors; viral-bacterial coinfection
PMID: 27736644 DOI: 10.1016/j.chom.2016.09.005
[PubMed - in process]
[h=1]Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality.[/h] Talmi-Frank D[SUP]1[/SUP], Altboum Z[SUP]2[/SUP], Solomonov I[SUP]3[/SUP], Udi Y[SUP]3[/SUP], Jaitin DA[SUP]2[/SUP], Klepfish M[SUP]3[/SUP], David E[SUP]2[/SUP], Zhuravlev A[SUP]3[/SUP], Keren-Shaul H[SUP]2[/SUP], Winter DR[SUP]2[/SUP], Gat-Viks I[SUP]4[/SUP], Mandelboim M[SUP]5[/SUP], Ziv T[SUP]6[/SUP], Amit I[SUP]7[/SUP], Sagi I[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage. MT1-MMP inhibition did not significantly alter the immune response or cytokine expression. The available flu therapeutic Oseltamivir did not prevent lung ECM damage and was less effective than anti-MT1-MMP in influenza virus Streptococcus pneumoniae coinfection paradigms. Combination therapy of Oseltamivir with anti-MT1-MMP showed a strong synergistic effect and resulted in complete recovery of infected mice. This study highlights the importance of tissue resilience in surviving infection and the potential of such host-pathogen therapy combinations for respiratory infections.
Copyright ? 2016 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] ECM remodeling; Influenza virus; MT1-MMP; host-pathogen gene regulation; immune genomics; matrix metalloproteinase inhibitors; viral-bacterial coinfection
PMID: 27736644 DOI: 10.1016/j.chom.2016.09.005
[PubMed - in process]