Alveolar barrier disruption in varicella pneumonia is associated with neutrophil extracellular trap formation
| العنوان: | Alveolar barrier disruption in varicella pneumonia is associated with neutrophil extracellular trap formation |
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| المؤلفون: | Mark W. Delany, Arno C. Andeweg, Wilfred F. J. van IJcken, Georges M. G. M. Verjans, Fatiha Zaaraoui-Boutahar, Henk-Jan van den Ham, Jeroen J. A. van Kampen, Werner J. D. Ouwendijk, Rory D. de Vries, Tamana Mehraban, Gijsbert P. van Nierop, Judith M. A. van den Brand |
| المساهمون: | Virology, Cell biology |
| المصدر: | JCI Insight, Vol 5, Iss 21 (2020) JCI insight, 5(21):e138900. The American Society for Clinical Investigation JCI Insight |
| بيانات النشر: | American Society for Clinical investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Herpesvirus 3, Human, Pulmonology, Neutrophils, viruses, Acute Lung Injury, Viremia, Lung injury, Virus Replication, Extracellular Traps, Simian varicella virus, Virus, Pathogenesis, Virology, Animals, Humans, Medicine, Innate immunity, Molecular pathology, Lung, biology, business.industry, General Medicine, Neutrophil extracellular traps, Viral Load, respiratory system, medicine.disease, biology.organism_classification, Macaca mulatta, Immunity, Innate, respiratory tract diseases, Disease Models, Animal, Pneumonia, medicine.anatomical_structure, Case-Control Studies, Varicella Zoster Virus Infection, Immunology, Female, business, Research Article |
| الوصف: | Primary varicella-zoster virus (VZV) infection in adults is often complicated by severe pneumonia, which is difficult to treat and is associated with high morbidity and mortality. Here, the simian varicella virus (SVV) nonhuman primate (NHP) model was used to investigate the pathogenesis of varicella pneumonia. SVV infection resulted in transient fever, viremia, and robust virus replication in alveolar pneumocytes and bronchus-associated lymphoid tissue. Clearance of infectious virus from lungs coincided with robust innate immune responses, leading to recruitment of inflammatory cells, mainly neutrophils and lymphocytes, and finally severe acute lung injury. SVV infection caused neutrophil activation and formation of neutrophil extracellular traps (NETs) in vitro and in vivo. Notably, NETs were also detected in lung and blood specimens of varicella pneumonia patients. Lung pathology in the SVV NHP model was associated with dysregulated expression of alveolar epithelial cell tight junction proteins (claudin-2, claudin-10, and claudin-18) and alveolar endothelial adherens junction protein VE-cadherin. Importantly, factors released by activated neutrophils, including NETs, were sufficient to reduce claudin-18 and VE-cadherin expression in NHP lung slice cultures. Collectively, the data indicate that alveolar barrier disruption in varicella pneumonia is associated with NET formation. A key role for neutrophil activation and impaired alveolar epithelial-endothelial barrier integrity is identified in the pathogenesis of varicella pneumonia. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbce390f9744809c978ec9bbbe4e02a0Test https://doaj.org/article/dac672c1f2874d9dbc53c40eca4bb8cdTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fbce390f9744809c978ec9bbbe4e02a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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