Abstract
The human pneumovirus respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract disease in young children worldwide. A hallmark of severe human RSV infection is the strong neutrophil recruitment to the airways and lungs. Massive neutrophil activation has been proven detrimental in numerous diseases, yet in RSV the contribution of neutrophils to disease severity, and thereby, the relevance of targeting them, is largely unknown. To determine the relevance of potential neutrophil targeting therapies, we implemented antibody-mediated neutrophil depletion in a mouse pneumonia virus of mice (PVM) model. PVM is a host specific murine pneumovirus closely related to human RSV, which reproduces many of the features of RSV infection, such as high viral replication and neutrophil recruitment. Clinical disease and markers of lung inflammation and injury were studied in PVM-infected mice treated with either depleting or isotype control antibodies. To confirm our results we performed all experiments in two mice strains: C57Bl6 and BALBc mice. Neutrophil depletion in blood and lungs was efficient throughout the disease. Remarkably, in both mouse strains we found no difference in clinical disease severity between neutrophil-depleted and control arms. In line with this observation, we found no differences between groups in histopathological lung injury and lung viral loads. In conclusion, our study shows that in mice neutrophil recruitment to the lungs does not affect disease outcome or viral clearance during severe PVM infection. As such, this model does not support the notion that neutrophils play a key role in mouse pneumovirus disease.
Highlights
The human pneumovirus respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young children worldwide [1,2,3]
In this severe pneumovirus disease model, neutrophil depletion by the specific antiLy6G 1A8 mAb resulted in significant depletion in blood and BAL in both C57Bl6 and BALBc mice (Fig 1A and 1B)
Neutrophil depletion in blood remained constant throughout the course of pneumonia virus of mice (PVM) disease (S2 Fig)
Summary
The human pneumovirus respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young children worldwide [1,2,3]. Neutrophils in Pneumovirus-Induced Lung Disease study, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Severe RSV disease and approximately 10% of these children need mechanical ventilation to survive [3]. Many of these mechanically-ventilated children fulfil the clinical criteria for acute respiratory distress syndrome (ARDS) at some point during their admission [4]. It is imperative to gain more insight into the key pathogenic mechanisms of human RSV infection in order to develop new therapeutics
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