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

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Matrix metalloproteinase-9 (MMP-9) is a key enzyme in inflammatory and injury responses.
• The role of MMP-9 in influenza A viral (IAV) infections is not fully understood.

Purpose of the Study:

• To investigate the role of MMP-9 in IAV infection pathogenesis.
• To evaluate MMP-9 as a potential therapeutic target for IAV.

Main Methods:

• Assessed plasma and lung MMP-9 levels in IAV-infected patients and mice.
• Utilized wild-type (WT) and Mmp-9 knockout (Mmp-9-/-) mice for infection studies.
• Analyzed immune cell populations, viral titers, lung injury markers, and cell shedding in bronchoalveolar lavage fluid (BALF).
• Conducted bone marrow-chimera studies and in vitro experiments with lung epithelial cells.

Main Results:

• Elevated MMP-9 levels were observed in IAV-infected patients and murine lungs.
• Mmp-9-/- mice exhibited reduced mortality, weight loss, lung viral titers, and lung injury compared to WT mice.
• Mmp-9 deficiency led to an altered immune response, including increased Th1-like T cells and reduced regulatory T cells.
• MMP-9 deficiency in lung parenchymal cells protected against IAV-induced mortality, and Mmp-9-/- lung epithelial cells showed lower viral loads in vitro.

Conclusions:

• MMP-9 plays a detrimental role in IAV pathogenesis, contributing to lung injury and mortality.
• MMP-9 deficiency confers protection against IAV by enhancing adaptive immunity and reducing epithelial barrier damage.
• MMP-9 is identified as a potential novel therapeutic target for influenza A viral infections.