Fig. 6.

NLRX1-mediated recognition of IAV PB1-F2 accessory protein protects Mφ mitochondria and enhances innate antiviral immunity. After early replication in airway epithelial cells, IAV virions are released in the airways, where they encounter and infect alveolar Mφ. IAV virus proapoptotic PB1-F2 accessory protein enters the mitochondria and induces apoptosis of infected Mφ, thereby suppressing early antiviral immunity, including type I IFN production. This immune evasion strategy is counteracted by the host mitochondrial PRR NLRX1, which binds to PB1-F2 and prevents apoptosis of infected Mφ. Enhanced survival of alveolar Mφ increases their antiviral functions and capacity to restrict viral replication, thus maintaining a protective balance between antiviral immunity and excessive inflammation.