{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:24:15Z","timestamp":1783056255409,"version":"3.54.6"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["25407"],"award-info":[{"award-number":["25407"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["123336"],"award-info":[{"award-number":["123336"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1RO1GM133961\u201001A1"],"award-info":[{"award-number":["1RO1GM133961\u201001A1"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although sepsis in burn patients is a major contributor to mortality, treatments are not always effective and underlying mechanisms have yet to be completely elucidated. NLRP3 inflammasome orchestrates burn\u2010induced, inflammatory\u2010driven pathophysiologic processes. Here, we determined the mechanism of NLRP3 inflammasome activation on bacterial clearance and mortality in burn sepsis. We obtained tissue and blood from 30 wild\u2010type and 30\u00a0<jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Mice were subjected to a two\u2010hit model of 25\u201330% TBSA scald burn followed by <jats:italic>Pseudomonas aeruginosa<\/jats:italic> wound infection 72\u00a0hours after injury. We also obtained tissue from 34 adult burn patients (\u226518\u00a0years of age) with early (0\u201311\u00a0days post\u2010burn) and later (\u226512\u00a0days post\u2010burn) surgical time\u2010points and ten healthy controls. Murine studies indicated that <jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> had 30% improved survival and bacterial clearance at the site of injury and is systemically relative to burn sepsis wild type. Greater macrophage and neutrophil infiltration occurred acutely after infection (12\u00a0hours) to the site of injury and adipose tissue. This was followed by increased macrophage and neutrophil infiltration to lymphoid organs and liver beyond the acute phase (24 and 72\u00a0hours). Interestingly, <jats:italic>Nlrp3<\/jats:italic> ablation increased acute systemic inflammation (IL\u20106, TNF\u2010\u03b1, IL\u20101\u03b2). Septic burn patients had persistently increased adipose NLRP3 by\u2010product expression beyond the acute phase that was more pronounced in late\u2010onset sepsis. Our findings suggest that <jats:italic>Nlrp3<\/jats:italic>\u00a0genetic ablation enhanced acute tissue\u2010specific inflammatory responsiveness. Likely, this occurs by paradoxically increasing acute immune infiltration and inflammation with a non\u2010persistent response. Clinically, persistent NLRP3\u2010mediated inflammation occurs in septic versus normal burn patients and potentially detrimentally impacts patient outcomes.<\/jats:p>","DOI":"10.1111\/imm.13427","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T03:39:47Z","timestamp":1636774787000},"page":"195-205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["NLRP3 knockout enhances immune infiltration and inflammatory responses and improves survival in a burn sepsis model"],"prefix":"10.1111","volume":"165","author":[{"given":"Mile","family":"Stanojcic","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roohi","family":"Vinaik","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdikarim","family":"Abdullahi","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chen","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-1664","authenticated-orcid":false,"given":"Marc\u00a0G.","family":"Jeschke","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute  Toronto Ontario Canada"},{"name":"Department of Surgery Division of Plastic Surgery University of Toronto  Toronto Ontario Canada"},{"name":"Department of Immunology University of Toronto  Toronto Ontario Canada"},{"name":"Ross Tilley Burn Centre Sunnybrook Health Sciences Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc8170"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.19.2.403-434.2006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2119\/2007-00132.Finnerty"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc6102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0704382"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1996.0312"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0000000000000337"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70001-X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.BCR.0000203493.31642.79"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.01.016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.02.003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-10614-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.008"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.009"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2022"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2009.00048"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12384"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000209"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002097"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2019.11.002"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33486-9"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2015.12.075"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201604-0892OC"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0b013e3181599bc9"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-332-1:95"},{"key":"e_1_2_10_29_1","first-page":"1","article-title":"Stress hyperglycemia, insulin treatment, and innate immune cells. Int","volume":"2014","author":"Xiu F","year":"2014","journal-title":"J Endocrinol"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.08.025"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.07.005"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa116"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302752"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.002"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.022"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12971"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13427","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13427","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:13:50Z","timestamp":1693196030000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/imm.13427"],"URL":"https:\/\/doi.org\/10.1111\/imm.13427","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,24]]},"assertion":[{"value":"2021-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}