Influenza lung injury: mechanisms and therapeutic opportunities

Abstract

In this Perspectives, we discuss some recent developments in the pathogenesis of acute lung injury following influenza infection, with an emphasis on promising therapeutic leads. Damage to the alveolar-capillary barrier has been quantified in mice, and agents have been identified that can help to preserve barrier integrity, such as vasculotide, angiopoietin-like 4 neutralization, and sphingosine 1-phosphate mimics. Results from studies using mesenchymal stem cells have been disappointing, despite promising data in other types of lung injury. The roles of fatty acid binding protein 5, prostaglandin E2, and the interplay between IFN-γ and STAT1 in epithelial signaling during infection have been addressed in vitro. Finally, we discuss the role of autophagy in inflammatory cytokine production and the viral life cycle and the opportunities this presents for intervention.

Keywords: acute lung injury; autophagy; influenza; signaling.

Fig. 1.

Role of autophagy in cytokine induction and viral budding. H5 protein activates autophagy by inhibiting the repressive Akt cascade and induces cytokine production via p38 MAPK. M2 prevents fusion of autophagosomes with lysosomes and relocates LC3 to the plasma membrane. IAV, influenza A virus; mTOR, mammalian target of rapamycin; 3-MA, 3-methylacetate; TSC, tuberous sclerosis complex. See text for further details.