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PLoS Genet ; 17(3): e1009383, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33657091

RESUMEN

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.


Asunto(s)
Infecciones Bacterianas/metabolismo , Señales (Psicología) , Resistencia a la Enfermedad/inmunología , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Hierro/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Autofagia , Infecciones Bacterianas/etiología , Caenorhabditis elegans , Resistencia a la Enfermedad/genética , Susceptibilidad a Enfermedades , Ferritinas/metabolismo , Interacciones Huésped-Patógeno/genética , Humanos , Modelos Biológicos , Salmonella typhimurium/inmunología
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