Neutrophils regulate the lung inflammatory response via γδ T cell infiltration in an experimental mouse model of human metapneumovirus infection

Neutrophils are the most abundant leukocytes in human circulation. They are the first immune cell population recruited to the sites of infection. However, the role of neutrophils to regulate host immune responses during respiratory viral infections is largely unknown. To elucidate the role of neutrophils in respiratory antiviral defense, we used an experimental mouse model of human metapneumovirus (HMPV) infection. HMPV, a member of the Paramyxoviridae family, is a leading respiratory pathogen causing severe symptoms, such as bronchiolitis and pneumonia, in young, elderly, and immunocompromised patients. We demonstrate that neutrophils are the predominant population of immune cells recruited into the lungs after HMPV infection. This led us to hypothesize that neutrophils represent a key player of the immune response during HMPV infection, thereby regulating HMPV-induced lung pathogenesis. Specific depletion of neutrophils in vivo using a mAb and simultaneous infection with HMPV exhibited higher levels of inflammatory cytokines, pulmonary inflammation, and severe clinical disease compared with HMPV-infected, competent mice. Interestingly, the lack of neutrophils altered gamma delta T cell accumulation in the lung. The absence of gamma delta T cells during HMPV infection led to reduced pulmonary inflammation. These novel findings demonstrate that neutrophils play a critical role in controlling HMPV-induced inflammatory responses by regulating gamma delta T cell infiltration to the site of infection.