{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:53:46Z","timestamp":1792785226801,"version":"4.5.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"19","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81420108022"],"award-info":[{"award-number":["81420108022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671967"],"award-info":[{"award-number":["81671967"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501703"],"award-info":[{"award-number":["81501703"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871594"],"award-info":[{"award-number":["81871594"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670853"],"award-info":[{"award-number":["31670853"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571551"],"award-info":[{"award-number":["81571551"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20190053"],"award-info":[{"award-number":["BK20190053"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology of Program of Suzhou","award":["SYS2018067"],"award-info":[{"award-number":["SYS2018067"]}]},{"name":"Pediatric Solid Tumor Multidisciplinary Team","award":["SZYJTD201706"],"award-info":[{"award-number":["SZYJTD201706"]}]},{"name":"Pediatric Precise Surgical Clinical Medical Center of Suzhou","award":["SZZXJ201505"],"award-info":[{"award-number":["SZZXJ201505"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,5,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Disease resistance and tolerance are evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered before the start of infection confers protection against polymicrobial sepsis by promoting resistance and tolerance. Notably, taurolidine given after the onset of infection also rescues mice from sepsis-associated lethality by enhancing disease tolerance to organ damage. This protection relies on an intact autophagy pathway, as taurolidine fails to protect autophagy-deficient mice against microbial sepsis. Specifically, taurolidine induces light chain 3-associated phagocytosis, but not xenophagy, in macrophages, resulting in an augmented bactericidal activity with enhanced cellular resistance to infection. These results highlight the importance of autophagy induction for taurolidine-augmented host resistance and disease tolerance and subsequent protection.<\/jats:p>","DOI":"10.1073\/pnas.2121244119","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T14:17:00Z","timestamp":1651760220000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance"],"prefix":"10.1073","volume":"119","author":[{"given":"Jie","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8187-5997","authenticated-orcid":false,"given":"Michael","family":"Ita","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-5391","authenticated-orcid":false,"given":"Huiting","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fara","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjiang","family":"Bai","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Peter","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Paul","family":"Redmond","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang Huai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research, Children\u2018s Hospital of Soochow University, Suzhou 215025, China"},{"name":"Department of Pediatric Surgery, Children\u2019s Hospital of Soochow University, Suzhou 215025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2006.08.015"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021333"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022139"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.04.001"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2432"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214935"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(03)00080-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.10.002"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06246"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.py.09.090171.001315"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.083782"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1148526"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001118"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.018"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12063"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01381.x"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09782"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.009"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.06.001"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06421"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811045106"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2019.04.012"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.222984"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800810743"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2004.06.006"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10434-000-0685-6"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jso.20827"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2566"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.2.7404"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003004"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1980"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.3"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/45257"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.080796"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3192"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113421108"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707792114"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001769"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.039"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.012"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.01.018"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003872"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.214"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.1020"},{"issue":"73","key":"e_1_3_4_48_2","first-page":"e50062","article-title":"An in\u00a0vivo assay to test blood vessel permeability","author":"Radu M.","year":"2013","unstructured":"M. Radu, J. Chernoff, An in\u00a0vivo assay to test blood vessel permeability. J. Vis. Exp. (73), e50062 (2013).","journal-title":"J. Vis. Exp."},{"issue":"139","key":"e_1_3_4_49_2","first-page":"57037","article-title":"An optimized Evans blue protocol to assess vascular leak in the mouse","author":"Wick M. J.","year":"2018","unstructured":"M. J. Wick, J. W. Harral, Z. L. Loomis, E. C. Dempsey, An optimized Evans blue protocol to assess vascular leak in the mouse. J. Vis. Exp. (139), 57037 (2018).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.12.015"},{"issue":"140","key":"e_1_3_4_51_2","first-page":"57032","article-title":"In vitro and in\u00a0vivo approaches to determine intestinal epithelial cell permeability","author":"Li B. R.","year":"2018","unstructured":"B. R. Li , In vitro and in\u00a0vivo approaches to determine intestinal epithelial cell permeability. J. Vis. Exp. (140), 57032 (2018).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.014"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2121244119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T14:19:18Z","timestamp":1651760358000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2121244119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":52,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,5,10]]}},"alternative-id":["10.1073\/pnas.2121244119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2121244119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]},"assertion":[{"value":"2021-12-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2121244119"}}