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However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan <jats:italic>Caenorhabditis elegans<\/jats:italic> as a model, we demonstrate that infection with a pathogenic bacterium <jats:italic>Salmonella enterica<\/jats:italic> serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of <jats:italic>ftn-1<\/jats:italic> and <jats:italic>ftn-2<\/jats:italic> encoding two H-ferritin subunits are upregulated upon <jats:italic>S<\/jats:italic>. 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 <jats:italic>S<\/jats:italic>. 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 <jats:italic>S<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009383","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:08:29Z","timestamp":1614798509000},"page":"e1009383","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection"],"prefix":"10.1371","volume":"17","author":[{"given":"Yi-Cheng","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Li","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei-Bei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-3841","authenticated-orcid":true,"given":"Yu-Qiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Ran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke-Qin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5519-4402","authenticated-orcid":true,"given":"Cheng-Gang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"issue":"5","key":"pgen.1009383.ref001","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.chom.2013.04.010","article-title":"Iron in infection and immunity","volume":"13","author":"JE Cassat","year":"2013","journal-title":"Cell host & microbe."},{"issue":"8","key":"pgen.1009383.ref002","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nri3863","article-title":"Iron homeostasis in host defence and inflammation","volume":"15","author":"T Ganz","year":"2015","journal-title":"Nature reviews Immunology"},{"issue":"5 Suppl 1","key":"pgen.1009383.ref003","doi-asserted-by":"crossref","first-page":"1549S","DOI":"10.1093\/jn\/133.5.1549S","article-title":"Ferritin: at the crossroads of iron and oxygen metabolism","volume":"133","author":"EC Theil","year":"2003","journal-title":"The Journal of nutrition"},{"issue":"5","key":"pgen.1009383.ref004","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.mad.2012.03.003","article-title":"Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting ageing in the nematode C. elegans","volume":"133","author":"S Valentini","year":"2012","journal-title":"Mechanisms of ageing and development"},{"issue":"8","key":"pgen.1009383.ref005","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nchembio807","article-title":"The role of iron regulatory proteins in mammalian iron homeostasis and disease","volume":"2","author":"TA Rouault","year":"2006","journal-title":"Nature chemical biology"},{"key":"pgen.1009383.ref006","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.freeradbiomed.2018.06.037","article-title":"Transferrin and transferrin receptors update","volume":"133","author":"H. 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