Title |
Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model.
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Published in |
Clinical Science, August 2017
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DOI | 10.1042/cs20171006 |
Pubmed ID | |
Authors |
Hao Wang, Desiree Anthony, Selcuk Yatmaz, Odilia Wijburg, Catherine Satzke, Bruce Levy, Ross Vlahos, Steven Bozinovski |
Abstract |
Formyl peptide receptor 2 (Fpr2/ALX) coordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the pro-resolving actions of aspirin triggered-RvD1 (AT-RvD1) in an acute co-infection pneumonia model. Co-infection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of co-infected mice, and immunohistochemistry identified prominent Fpr2/ALX immunoreactivity in bronchial epithelial cells and macrophages. Levels of circulating and lung SAA were also highly increased in co-infected mice. Therapeutic treatment with exogenous AT-RvD1 during the acute phase of infection (day 4-6 post pneumococcal inoculation) significantly reduced the pneumococcal load. AT-RvD1 also significantly reduced neutrophil elastase activity and restored total antimicrobial activity in bronchoalveolar lavage fluid of co-infected mice. Pneumonia severity, as measured by quantifying parenchymal inflammation or alveolitis was significantly reduced with AT-RvD1 treatment, which also reduced the number of infiltrating lung neutrophils and monocytes/macrophages as assessed by flow cytometry. The reduction in distal lung inflammation in AT-RvD1 treated mice was not associated with a significant reduction in inflammatory and chemokine mediators. In summary, we demonstrate that in the co-infection setting, SAA levels were persistently increased and exogenous AT-RvD1 facilitated more rapid clearance of pneumococci in the lungs, whilst concurrently reducing the severity of pneumonia by limiting excessive leukocyte chemotaxis from the infected bronchioles to distal areas of the lungs. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 57 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 18% |
Researcher | 10 | 18% |
Student > Master | 7 | 12% |
Professor > Associate Professor | 4 | 7% |
Student > Postgraduate | 3 | 5% |
Other | 9 | 16% |
Unknown | 14 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 8 | 14% |
Biochemistry, Genetics and Molecular Biology | 8 | 14% |
Immunology and Microbiology | 7 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 11% |
Agricultural and Biological Sciences | 3 | 5% |
Other | 7 | 12% |
Unknown | 18 | 32% |