No abstract

In vitro studies demonstrated that optineurin, a ubiquitin (Ub)-binding protein, becomes an autophagy cargo receptor upon being phosphorylated on Ser177 by TANK binding kinase 1 (TBK1) in response to cytosolic Salmonella typhimurium. Phosphorylated optineurin then regulates autophagy by delivering ubiquinated bacteria to autophagosomal membranes via light chain 3 (LC3), hence restricting their growth. To test the in vivo relevance of these findings, we used a mouse model with C-terminal optineurin truncation, which lacks the Ub-binding region (Optn470T). No difference was found between WT and Optn470T macrophages in LC3 lipidation during LPS-induced autophagy. Similarly, p62+LC3+ aggresome-like structures generated upon LPS or Salmonella typhimurium stimulation in Optn470T macrophages colocalized with lysosomal marker LAMP1 to the same extent as in WT cells, demonstrating no perturbation in autophagosome fusion to lysosomes. Importantly, upon in vivo infection with Salmonella typhimurium, no difference was found in bacterial replication in WT and Optn470T mice. These results argue against the role of optineurin in Salmonella typhimurium infection in vivo.