Stabilization of epithelial integrity in influenza virus pneumonia: role of death ligands and their downstream effectors (Peteranderl / Wolff)
A hallmark of influenza virus (IV)-induced pneumonia is the structural and functional impairment of the alveolar epithelium caused by viral factors as well as soluble mediators including cell death-inducing ligands of the tumor necrosis factor (TNF) superfamily.
Here, we aim to
(i) elucidate how these death ligands and their downstream signaling contribute to IV disease progression
(ii) investigate the mechanisms by which SAMHD1, a factor activated by TNFα and IFN, supports virus propagation and,or hampers epithelial integrity, and
(iii) to define antagonistic strategies targeting death ligand-related signaling networks in in vivo models of IV-induced pneumonia and bacterial superinfection.