NMP4 regulates the innate immune response to influenza A virus infection
| Autor: | Jianguang Du, Shengping Huang, Joseph P. Bidwell, Michele Adaway, Jie Sun, Shuangshuang Yang, Baohua Zhou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chemokine Neutrophils Immunology Inflammation Adaptive Immunity CCL7 medicine.disease_cause Article Monocytes Immunomodulation 03 medical and health sciences Mice 0302 clinical medicine Immune system Nuclear Matrix-Associated Proteins Orthomyxoviridae Infections medicine Influenza A virus Immunology and Allergy Animals Mice Knockout Innate immune system biology Monocyte Immunity Innate CXCL1 Chemotaxis Leukocyte Disease Models Animal 030104 developmental biology medicine.anatomical_structure Host-Pathogen Interactions biology.protein Cytokines Disease Susceptibility medicine.symptom Inflammation Mediators 030215 immunology Transcription Factors |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | Severe influenza A virus infection typically triggers excessive and detrimental lung inflammation with massive cell infiltration and hyper-production of cytokines and chemokines. We identified a novel function for nuclear matrix protein 4 (NMP4), a zinc-finger-containing transcription factor playing roles in bone formation and spermatogenesis, in regulating antiviral immune response and immunopathology. Nmp4-deficient mice are protected from H1N1 influenza infection, losing only 5% body weight compared to a 20% weight loss in wild type mice. While having no effects on viral clearance or CD8/CD4 T cell or humoral responses, deficiency of Nmp4 in either lung structural cells or hematopoietic cells significantly reduces the recruitment of monocytes and neutrophils to the lungs. Consistent with fewer innate cells in the airways, influenza-infected Nmp4-deficient mice have significantly decreased expression of chemokine genes Ccl2, Ccl7 and Cxcl1 as well as pro-inflammatory cytokine genes Il1b and Il6. Furthermore, NMP4 binds to the promoters and/or conserved non-coding sequences of the chemokine genes and regulates their expression in mouse lung epithelial cells and macrophages. Our data suggest that NMP4 functions to promote monocyte- and neutrophil-attracting chemokine expression upon influenza A infection, resulting in exaggerated innate inflammation and lung tissue damage. |
| Databáze: | OpenAIRE |
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