Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial co-infection pneumonia model

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 chem...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research