Critical role of Neutrophils in Respiratory Syncytial Virus (RSV) induced disease pathogenesis (INC8P.440)

Neutrophils comprise the largest number of immune cells in the human body, and being the first immune cells to the site of injury and infection, neutrophils act as the first line of defense against harmful pathogens. RSV has been identified as a leading cause of respiratory tract illness in children worldwide. RSV induced disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia. The role of neutrophils in innate immune responses to RSV infection has not been fully characterized. We have employed anti-Ly6G clone monoclonal antibody 1A8 to specifically deplete neutrophils in Balb/c mice to study the role of neutrophils in RSV induced disease pathogenesis. Neutrophil depletion in mice infected with RSV A2 or Long strain caused a significant increase in body weight loss, airway hyper responsiveness and lung inflammation. Even though no effect on peak viral replication was observed; a significant reduction in early viral load and a delayed viral clearance in mice lacking neutrophils were observed. While depletion of neutrophils has no effect on the production of BAL type I IFNs, a significant increase in Th17 group of cytokines (IL-17A, IL-17F, IL-22, IL-23p19 and CD40L), G-CSF, KC and MIP-1β was observed. Moreover, we observed a significant reduction in lung DCs, pDCs and virus specific CD4 and CD8 cells in neutrophil depleted mice. Our study demonstrates that neutrophils play a critical role in disease progression of RSV infections.