{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:43:30Z","timestamp":1760150610981,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospices Civils de Lyon"},{"name":"Fondation HCL"},{"name":"Claude Bernard Lyon 1 University"},{"name":"R\u00e9gion Auvergne Rh\u00f4ne-Alpes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1\u03b2 and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients (n = 15) and bacterial septic shock patients (n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.<\/jats:p>","DOI":"10.3390\/v15122419","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:55:16Z","timestamp":1702457716000},"page":"2419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients"],"prefix":"10.3390","volume":"15","author":[{"given":"R\u00e9my","family":"Coudereau","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France"},{"name":"EA 7426 \u201cPathophysiology of Injury-Induced Immunosuppression\u201d (Universit\u00e9 Claude Bernard Lyon 1-Hospices Civils de Lyon-bioM\u00e9rieux), Joint Research Unit HCL-Biom\u00e9rieux, 69437 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Monneret","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France"},{"name":"EA 7426 \u201cPathophysiology of Injury-Induced Immunosuppression\u201d (Universit\u00e9 Claude Bernard Lyon 1-Hospices Civils de Lyon-bioM\u00e9rieux), Joint Research Unit HCL-Biom\u00e9rieux, 69437 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Claire","family":"Lukaszewicz","sequence":"additional","affiliation":[{"name":"EA 7426 \u201cPathophysiology of Injury-Induced Immunosuppression\u201d (Universit\u00e9 Claude Bernard Lyon 1-Hospices Civils de Lyon-bioM\u00e9rieux), Joint Research Unit HCL-Biom\u00e9rieux, 69437 Lyon, France"},{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Anesthesia and Critical Care Medicine Department, 69437 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9n\u00e9dicte F.","family":"Py","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard-Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Argaud","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Medical Intensive Care Department, 69002 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-9761","authenticated-orcid":false,"given":"Martin","family":"Cour","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Medical Intensive Care Department, 69002 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Bidar","sequence":"additional","affiliation":[{"name":"EA 7426 \u201cPathophysiology of Injury-Induced Immunosuppression\u201d (Universit\u00e9 Claude Bernard Lyon 1-Hospices Civils de Lyon-bioM\u00e9rieux), Joint Research Unit HCL-Biom\u00e9rieux, 69437 Lyon, France"},{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Anesthesia and Critical Care Medicine Department, 69437 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1930-8956","authenticated-orcid":false,"given":"Morgane","family":"Gossez","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard-Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0462-4235","authenticated-orcid":false,"given":"Fabienne","family":"Venet","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard-Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock 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