As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S . Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S . Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S . Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection. Author summary Iron, an essential nutrient for both hosts and pathogens, can impact host-pathogen interactions. Thus, depending on availability of iron, hosts may use distinct strategies to defend against bacterial infections. Using the model organism Caenorhabditis elegans , we show that autophagy is activated and required for resistance to S . Typhimurium infection under normal conditions. In the presence of exogenous iron, autophagy is suppressed, leading to an increase in the protein level of ferritin, which in turn protects worms against S . Typhimurium infection. Finally, our data demonstrate that TOR is a molecular switch for turning autophagy and ferritin on and off. Thus, our study reveals a previously unknown role of TOR in modulating the transition between autophagy and iron sequestration in response to a bacterial infection via sensing an iron cue.
【초록키워드】 Infection, ferritin, iron, molecular mechanism, autophagy, Rapamycin, Protein, survival, pathogen, Bacterial infection, target, Pathogens, molecular, Degradation, Bacterial infections, Salmonella, host defense, host-pathogen interactions, host innate immunity, Caenorhabditis elegans, pathogenic bacterium, essential nutrient, subunit, transition, transcripts, hosts, pathogenic, organism, protein level, Defense, regulator, worms, worm, transcript, Host, PROTECT, required, activated, modulate, increase in, induce, upregulated, suppressed, suppresse, reveal, conditions, turn, Increased, activating, Caenorhabditis elegan, defend, modulating, 【제목키워드】 molecular, function, Host,