Protective early innate immune activation by mitochondrial antiviral signalling protein (MAVS) in bacterial pneumonia

Mitochondrial antiviral signalling protein (MAVS) is important for host antiviral immunity and recent studies suggest its role in fungal defence. However, the role of MAVS in antibacterial host defence remains unclear. The Gram-negative bacterium non-typeable Haemophilus influenzae (NTHi) is the predominant pathogen in airway diseases. Using a murine infection model, we demonstrate that NTHi infection leads to the degradation of MAVS. MAVS deficiency results in compromised bacterial control during NTHi infection. Mavs-/- mice demonstrated impaired early production of proinflammatory cytokines and reduced maturation and activation of NK cells. Depletion of macrophages eliminated the disparity in bacterial loads and weight loss between the two mouse strains. Moreover, in vitro experiments using freshly isolated alveolar macrophages revealed that MAVS played an important role in macrophage function against bacterial infections by detecting bacterial RNA. Overall, our data support the involvement of MAVS signalling in early-stage antibacterial immunity both in vivo and in vitro.