Although neutrophil depletion in human RSV-infected mice showed that neutrophils mediate mucin expression and thereby potentially contribute to airway obstruction [22], models studying the effects of neutrophilic inflammation on lung permeability and injury during PVM infection were lacking. GUID:?C814BEBE-DF39-464A-BDE0-9A458C413383 S1 Supplemental Method: Animal housing and handling. (DOC) pone.0168779.s004.doc (23K) GUID:?014E6015-4A8C-4D35-B2EA-B6914E8037D4 S1 Table: Baseline animal characteristics. Iso; isotype control antibodies, 1A8; 1A8 monoclonal antibody, Weight in grams SD.(DOC) pone.0168779.s005.doc (36K) GUID:?3C693B79-3F3C-4042-B7C9-72E288B7DB35 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. 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 Klf6 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. Introduction The human pneumovirus respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young children worldwide [1C3]. Global mortality is estimated at almost 200,000 deaths per year in children under the age of 5 years, but occurs mainly in resource-limited countries [1]. In the US alone, 172,000 children are admitted annually to the hospital due to 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 HOI-07 their admission [4]. Currently, there is no licensed vaccine or effective therapeutic treatment for human RSV disease. It is imperative to gain more insight into the key HOI-07 pathogenic mechanisms of human RSV infection in order to develop new therapeutics. One of the key features seen during human RSV infection is influx of neutrophils into the airways and alveolar compartment of the lungs. Up to 76% of the cells present HOI-07 in the airways and lungs are neutrophils [5]. Additionally, post-mortem examination of lung tissue sections from fatal RSV cases predominantly shows neutrophilic infiltration with airway obstruction caused by neutrophil-rich mucus plugs [6]. Strong lung neutrophil recruitment is also observed in animal pneumovirus disease, such as bovine HOI-07 RSV infection in calves and pneumonia virus of mice (PVM) in rodents [7]. Both human and animal pneumovirus infections elicit prominent CXC chemokine responses, including CXCL-8 [8, 9] and KC [10], which likely contribute to the neutrophilic inflammation. However, so far it is unknown if these high numbers of neutrophils in the airways and lungs are solely protective or may also be detrimental during pneumovirus infections. On the one hand, neutrophils possess a broad arsenal of defensive strategies, including reactive.