title: Pneumovirus-Induced Lung Disease in Mice Is Independent of Neutrophil-Driven Inflammation.
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.
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital AMC, Amsterdam, The Netherlands.
authors.forename: Bart
authors.identifier: http://orcid.org/0000-0002-0289-4250
authors.initials: B
authors.lastname: Cortjens
authors.affiliation: Experimental Immunology and Respiratory Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Epirus Biopharmaceuticals Netherlands, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital AMC, Amsterdam, The Netherlands.
authors.forename: Reinout A
authors.initials: RA
authors.lastname: Bem
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital AMC, Amsterdam, The Netherlands.
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D018186:Pneumovirus Infections / Q000276:immunology* / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology