| RRC ID |
86971
|
| Author |
Okamori S, Ishii M, Asakura T, Suzuki S, Namkoong H, Kagawa S, Hegab AE, Yagi K, Kamata H, Kusumoto T, Ogawa T, Takahashi H, Yoda M, Horiuchi K, Hasegawa N, Fukunaga K.
|
| Title |
ADAM10 partially protects mice against influenza pneumonia by suppressing specific myeloid cell population.
|
| Journal |
Am J Physiol Lung Cell Mol Physiol
|
| Abstract |
The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene (Adam10)flox/flox/Lyz2-Cre (Adam10ΔLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10ΔLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-α, IL-1β, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10ΔLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocyte/macrophage-like phenotype, were significantly increased in the lungs of Adam10ΔLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10ΔLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10ΔLyz2 mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10ΔLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.
|
| Volume |
321(5)
|
| Pages |
L872-L884
|
| Published |
2021-11-1
|
| DOI |
10.1152/ajplung.00619.2020
|
| PMID |
34523355
|
| MeSH |
ADAM10 Protein / genetics
ADAM10 Protein / metabolism*
Adoptive Transfer / methods
Amyloid Precursor Protein Secretases / genetics
Amyloid Precursor Protein Secretases / metabolism*
Animals
Arginase / antagonists & inhibitors
Arginase / biosynthesis*
Bronchoalveolar Lavage Fluid / chemistry
Bronchoalveolar Lavage Fluid / cytology
Cytokines / analysis
Immunity, Innate / immunology
Influenza A Virus, H1N1 Subtype / metabolism*
Macrophages / immunology*
Macrophages / transplantation
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells / immunology*
Myeloid Cells / transplantation
Orthomyxoviridae Infections / mortality
Orthomyxoviridae Infections / pathology*
Orthomyxoviridae Infections / prevention & control
Prognosis
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
|
| IF |
4.418
|
| Resource |
| Mice |
RBRC02302 |
