Regulatory role of neutrophils in the inflammatory responses to paramyxovirus infection in mice
Abstract
Abstract Neutrophils are the most abundant leukocytes (50% to 70%) in humans and are the first immune cell population recruited to the sites of infection. They are known to act in the first line of innate immune defense against invading pathogens, and more recently, to playing a crucial role in orchestrating adaptive immune responses. However, the role of neutrophils in the control of adaptive immune response during respiratory viral infections is still largely unknown. In order to elucidate the role of neutrophils in respiratory antiviral defense, we employed an experimental mouse model of human metapneumovirus (hMPV) infection. HMPV is a member of the Paramyxoviridae family, and a leading respiratory pathogen causing severe symptoms such as bronchiolitis and pneumonia in the young, elderly and immunocompromised patients. Our findings demonstrate that neutrophils are rapidly recruited in high numbers to the lungs of infected mice (>80%) during the acute phase of infection. Specific depletion of neutrophil in vivo using a monoclonal antibody and simultaneous infection with hMPV exhibited significantly higher levels of inflammatory cytokines, pulmonary inflammation and severe clinical disease (as indicated by an enhanced body weight loss and clinical illness) compared to hMPV-infected competent mice. Interestingly, the lack of neutrophils altered the T cell responses in the lung, particularly the γδ-T-cell subset. Finally, we also observed that the recruitment of neutrophils to the lung was controlled by the expression of the hMPV attachment protein. These novel findings demonstrate that neutrophils regulate T cell responses and are critically important for the control of the hMPV-induced inflammatory responses in the respiratory tract.