Speakers
Details
ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral activity, however its role during bacterial infection had not been addressed. We found that Listeria infection leads to an early interferon-independent increase in ISG15 expression in non-phagocytic cells through the cytosolic surveillance pathway. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of Stable Isotope Labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. We are currently employing a murine model of hyper-ISGylation to further characterize the function of ISG15 during Listeria infection. Interestingly, this model has brought to light a liver-specific role of ISG15. In the future, we aim to address the fundamental question of how the cell responds to stress by decoding novel networks of covalent protein complexes, in particular during the response to infection, ER-stress and autophagy.
(Host : Alexei Korennykh / Contact: Anna Schmedel 8-5028)