Neutrophils in respiratory syncytial virus disease: Untangling the NET

Respiratory syncytial virus (RSV) is one of the most important causes of childhood pneumonia and bronchiolitis worldwide. The disease is accompanied by prominent neutrophilic inflammation of the airways. However, the precise role of these immune cells during the disease is largely unknown. The central focus of this thesis is the neutrophil, with the overall aim to increase our understanding of the role of this important innate immune cell in the pathogenesis of RSV lower respiratory tract disease (RSV-LRTD). In part I we go more into detail about two host-specific RSV animal models. We conclude that the bovine and human RSV model, together, mimic many aspects of human-RSV infection in young infants. In chapter 3 we explore another RSV animal model; the pneumonia virus of mice (PVM) model. We conclude that the PVM-model lacks activation of essential neutrophil effector functions needed to investigate the role of neutrophils during pneumovirus infections, this might be the explanation why we could not find any difference between neutrophil depleted and non-depleted mice in this RSV model. In chapter 4 we investigated if viral respiratory infections are accompanied by different neutrophil subsets and if these subsets could have either a suppressive phenotype or an activated phenotype. We could not find suppressive neutrophils in infants infected with virus alone, in contrast to infants with both viral and bacterial co-infection.
In chapter 5 we summarise what is known about NET formation during (paediatric) respiratory diseases. In chapter 6 we investigated whether RSV was able to induce NET formation by human neutrophils in vitro, and if these NETs could trap viral particles and aid in the anti-viral response to RSV. Chapter 7 describes the effect of local dornase alfa treatment in bovine RSV infected calves. We found significant NET degradation during dornase alfa treatment compared to the control group, these results support the notion that treatment of NET-rich mucusplugs could alleviate airway obstruction. In chapter 8 we describe the build-up and functional characteristics of a panel of G-specific antibodies retrieved from humans. We found that these antibodies target specific epitopes in and around the conserved region of the G protein.