ArticlePLoS pathogens2012
Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 205 citations in OpenAlex.
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- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- IL-27 signaling mediates skin inflammation in experimental psoriasis and atopic dermatitis.Cell & bioscience · 2026Article
- Redox-Dependent Activation of Matrix Metalloproteinases Regulates Influenza A Virus Replication in Neuronal Cells.International journal of microbiology · 2026Article
- 1-Deoxynojirimycin Combined with Theaflavins Targets PTGS2/MMP9 to Exert a Synergistic Hypoglycemic Effect.Nutrients · 2025Article
- Matrix Metalloproteinase-9 (MMP-9) as a Therapeutic Target: Insights into Molecular Pathways and Clinical Applications.Pharmaceutics · 2025Review
- Cellular and molecular characterisation of the peripheral immune environment in migraine.Pain reports · 2025Article
- Impact of platelet transfusions on plasma proteomes in controlled endotoxemia and in hemato-oncological patients.Transfusion · 2025Article
- ZBP1-driven cell death in severe influenza.Trends in microbiology · 2025Review
- Heparanase-induced endothelial glycocalyx degradation exacerbates lung ischemia/reperfusion injury in male mice.Physiological reports · 2024Article
- Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectives.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Beyond troponins: Emerging diagnostic significance of novel markers in NSTEMI.Global cardiology science & practice · 2024Article
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.American journal of physiology. Cell physiology · 2024Review
- Proteolytic Vesicles Derived fromBiomedicines · 2024Article
- The Inovirus Pf4 Triggers Antiviral Responses and Disrupts the Proliferation of Airway Basal Epithelial Cells.Viruses · 2024Article
- Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.JCI insight · 2024Article
- Matrix metalloproteinases mediate influenza A-associated shedding of the alveolar epithelial glycocalyx.PloS one · 2024Article
- Whole blood transcriptomics reveals granulocyte colony-stimulating factor as a mediator of cardiopulmonary bypass-induced systemic inflammatory response syndrome.Clinical & translational immunology · 2024Article
- IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection.Nature communications · 2023Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP) 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR) signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88⁻/⁻ airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.