Figure 7. Schematic diagram of the mechanism of indirubin-induced attenuation of H1N1 pathogenesis in the susceptible model.

MAVS localizes to mitochondria to exert an anti-viral effect. H1N1 infection triggers host cell activation of the NF-κB and IRF3 signaling pathway following MAVS sensing. STING acts as a mitochondria cofactor for MAVS signaling to promote NF-κB and IRF3 production. CORT impacts the function of mitochondria, which has adverse effects on MAVS signaling. Indirubin promotes the production of IFN-β and IFITM3 by recovering MAVS signaling and maintaining mitochondrial function affected by CORT in the susceptible model. Moreover, indirubin is found to promote MAVS signaling by regulating STING following influenza A virus infection. In addition, indirubin attenuates NF-κB dependent pro-inflammatory cytokine production to alleviate pneumonia in restraint-stressed mice.