Unknown

Dataset Information

0

Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection.


ABSTRACT: Matrix metalloproteinase-9 (MMP-9) cleaves various proteins to regulate inflammatory and injury responses. However, MMP-9's activities during influenza A viral (IAV) infections are incompletely understood. Herein, plasma MMP-9 levels were increased in patients with pandemic H1N1 and seasonal IAV infections. MMP-9 lung levels were increased and localized to airway epithelial cells and leukocytes in H1N1-infected WT murine lungs. H1N1-infected Mmp-9-/- mice had lower mortality rates, reduced weight loss, lower lung viral titers, and reduced lung injury, along with lower E-cadherin shedding in bronchoalveolar lavage fluid (BALF) samples than WT mice. H1N1-infected Mmp-9-/- mice had an altered immune response to IAV with lower BALF PMN and macrophage counts, higher Th1-like CD4+ and CD8+ T cell subsets, lower T regulatory cell counts, reduced lung type I interferon levels, and higher lung interferon-? levels. Mmp-9 bone marrow-chimera studies revealed that Mmp-9 deficiency in lung parenchymal cells protected mice from IAV-induced mortality. H1N1-infected Mmp-9-/- lung epithelial cells had lower viral titers than H1N1-infected WT cells in vitro. Thus, H1N1-infected Mmp-9-/- mice are protected from IAV-induced lung disease due to a more effective adaptive immune response to IAV and reduced epithelial barrier injury due partly to reduced E-cadherin shedding. Thus, we believe that MMP-9 is a novel therapeutic target for IAV infections.

SUBMITTER: Rojas-Quintero J 

PROVIDER: S-EPMC6338318 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC5892427 | BioStudies
2020-01-01 | S-EPMC7456638 | BioStudies
2018-01-01 | S-EPMC5962662 | BioStudies
2010-01-01 | S-EPMC2938777 | BioStudies
2016-01-01 | S-EPMC4753462 | BioStudies
2017-01-01 | S-EPMC5454420 | BioStudies
1000-01-01 | S-EPMC6286381 | BioStudies
2011-01-01 | S-EPMC3197947 | BioStudies
2018-01-01 | S-EPMC5966536 | BioStudies
2017-01-01 | S-EPMC5507541 | BioStudies