Researchers from the Institut Pasteur, Inserm, INRA and the University of Freiburg have uncovered the key role played by the protein ISG15 in the fight against bacterial infections. During listeria infection, this protein promotes the release of cytokines which help the body eliminate the bacteria.
When human cells are infected by an invading microbe, they activate a defensive program which produces hundreds of genes. Some of these genes have been described to have anti-viral or anti-bacterial functions, while others remain relatively understudied. One such protein is called ISG15. ISG15 is a biubiquitin-protein that can chemically attach to other proteins and is known to help cells fight viral infections. However, it is not clear what role ISG15 plays in fighting bacterial infections.
In this work, researchers from the Institut Pasteur, Inserm, INRA and the University of Freiburg studied the role of ISG15 in human cells exposed to Listeria monocytogenes, a bacterium that can cause serious food poisoning in humans. The bacteria infect cells in the lining of the human gut. Cells that detect the bacteria respond by producing proteins called Interferons and other signaling proteins that activate the body’s immune system to fight the infection. Typically, ISG15 is produced following Interferon. However, the research work carried out by Dr Lilliana Radoshevich, from the Bacteria-Cell Interactions Unit led by Prof. Pascale Cossart at the Institut Pasteur, indicates that the initial ISG15 production does not depend on Interferon proteins. Instead, ISG15 production is triggered by an alternative pathway called the cytosolic surveillance pathway, which is activated by the presence of bacterial DNA inside the cell.
Further experiments determined that ISG15 can counteract Listeria infections both in cells grown in culture, and in vivo. Strikingly, ISG15 modifies proteins in the cell to promote the release of proteins called cytokines that help the body to eliminate the bacteria. These findings reveal a new role for ISG15 in fighting bacterial infections and bring to light a number of interesting avenues to explore in future studies. Next steps will determine how ISG15 modulates cytokine secretion. Ultimately, ISG15 is important for viral and bacterial infection and its levels are increased in human cancers, therefore in the future being able to modulate its activity could be a promising therapeutic strategy for a number of important human diseases.
ISG15 counteracts Listeria monocytogenes infection, eLife, August 11, 2015
Lilliana Radoshevich (Institut Pasteur), Francis Impens (Institut Pasteur), David Ribet (Institut Pasteur), Juan Quereda (Institut Pasteur), To Nam Tham (Institut Pasteur), Marie-Anne Nahori (Institut Pasteur), Hélène Bierne (AgroParisTech), Olivier Dussurget (Institut Pasteur), Javier Pizarro-Cerdá (Institut Pasteur), Klaus-Peter Knobeloch (Universitätsklinikum Freiburg), et Pascale Cossart (Institut Pasteur)
Mis à jour le 11/08/2015