Examining the Role of Neutrophils in Respiratory Syncytial Virus (RSV) Infection (168.26)

Abstract

Abstract The inflammatory process in the respiratory tracts of respiratory syncytial virus (RSV)-infected infants is not well characterized. Respiratory syncytial virus infects bronchial epithelial cells, resulting in epithelial activation and damage and an increased neutrophil response. However, the role of neutrophils in RSV pathogenesis is not known. To examine their role, we used a monoclonal antibody to Ly6G to deplete neutrophils in BALB/c mice infected with an RSV clinical isolate. Mice were then examined for weight loss, viral load, cytokine production, mucus production, and lung pathology. Administration of anti-Ly6G resulted in depletion of neutrophils from RSV-infected mice in blood and lungs. Neutrophil-depleted, RSV-infected animals lost more weight than infected isotype-control treated animals. There was, however, no significant effect on viral load. Neutrophil-depleted, RSV-infected mice produced less mucin than isotype-treated, RSV-infected mice. Neutrophil depletion during RSV infection also resulted in decreased TNF-α, IL-13, IL-4 and MIP-1α levels in the lung. Neutrophil depletion during RSV infection resulted in greater bronchiolar and alveolar edema, perivascular cuffing, alveolar hemorrhage, and vasculitis compared to control-treated, RSV-infected mice. This data shows that neutrophils play a major immune modulation role in RSV infection, promoting TH2 cytokine expression and airway mucus expression but also protecting against lung damage and disease severity.