{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:02:49Z","timestamp":1791842569615,"version":"4.3.4"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,26]]},"abstract":"<jats:p>\n                    Inflammasomes are intracellular multiprotein signaling complexes that activate Caspase-1, leading to the cleavage and secretion of IL-1\u03b2 and IL-18, and ultimately host cell death. Inflammasome activation is a common cellular response to infection; however, the consequences of inflammasome activation during acute infection and in the development of long-term protective immunity is not well understood. To investigate the role of the inflammasome in vivo, we engineered a strain of\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    that ectopically expresses\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    flagellin, a potent activator of the Nlrc4 inflammasome. Compared with wild-type\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    , strains that ectopically secreted flagellin induced robust host cell death and IL-1\u03b2 secretion. These strains were highly attenuated both in bone marrow-derived macrophages and in vivo compared with wild-type\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    . Attenuation in vivo was dependent on Nlrc4, but independent of IL-1\u03b2\/IL-18 or neutrophil activity.\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    strains that activated the inflammasome generated significantly less protective immunity, a phenotype that correlated with decreased induction of antigen-specific T cells. Our data suggest that avoidance of inflammasome activation is a critical virulence strategy for intracellular pathogens, and that activation of the inflammasome leads to decreased long-term protective immunity and diminished T-cell responses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1019041108","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T02:10:10Z","timestamp":1310436610000},"page":"12419-12424","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["<i>Listeria monocytogenes<\/i>\n                    engineered to activate the Nlrc4 inflammasome are severely attenuated and are poor inducers of protective immunity"],"prefix":"10.1073","volume":"108","author":[{"given":"John-Demian","family":"Sauer","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Pereyre","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and"},{"name":"Laboratoire de Bacteriologie, University of Bordeaux, EA 3671, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina A.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Hanson","sequence":"additional","affiliation":[{"name":"Aduro BioTech, Berkeley, CA 94710; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lauer","sequence":"additional","affiliation":[{"name":"Aduro BioTech, Berkeley, CA 94710; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology and"},{"name":"School of Public Health, University of California, Berkeley, CA 94720-3202;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,7,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1183021"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132715"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1346"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1344"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1646"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913087107"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051659"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050977"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001222"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.06.005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081667"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902477"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06939"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.11.2822-2829.1987"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.4.1597"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.12.6754-6765.2003"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7558"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.04.004"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610762200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04515"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4337"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901346"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1864"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.259"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6441-6448.2005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80209-5"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.5.2585-2589.1999"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737532"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1461"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.120.1.93"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404924101"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1960"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh041"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.7.3869"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041214"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.017"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838718"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00365-5"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.12.5608-5613.1994"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.4.1459"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1019041108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:12:20Z","timestamp":1649794340000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1019041108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7,11]]},"references-count":41,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2011,7,26]]}},"alternative-id":["10.1073\/pnas.1019041108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1019041108","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.12217956.13384054","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7,11]]},"assertion":[{"value":"2011-07-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}