TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection

• Published in: PLoS genetics Vol. 17; no. 3; p. e1009383
• Main Authors: Ma, Yi-Cheng, Dai, Li-Li, Qiu, Bei-Bei, Zhou, Ying, Zhao, Yu-Qiang, Ran, Yu, Zhang, Ke-Qin, Zou, Cheng-Gang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.03.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Autophagy; Bacterial infections; Biology and Life Sciences; Cell death; Chelation; Colonization; Control; Defecation; Dietary supplements; E coli; Experiments; Ferritin; Health aspects; Homeostasis; Host-bacteria relationships; Infections; Iron; Iron in the body; Kinases; Medicine and Health Sciences; Metabolism; Molecular microbiology; Mortality; Natural immunity; Pharynx; Physical Sciences; Physiological aspects; Proteins; Rapamycin; Research and Analysis Methods; Salmonellosis; Transcription; Worms; China
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009383

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.