{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:04:11Z","timestamp":1791345851829,"version":"4.3.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,6,3]]},"abstract":"<jats:p>\n                    NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1\u03b2. Yet, the molecular mechanism by which NOD2 can stimulate IL-1\u03b2 secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1\u03b2 processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly,\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    infection induces IL-1\u03b2 secretion in a manner that depended on caspase-1 and NOD2.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , Anthrax lethal toxin strongly potentiated IL-1\u03b2 secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    -induced inflammatory response by being a critical mediator of IL-1\u03b2 secretion.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0802726105","type":"journal-article","created":{"date-parts":[[2008,5,29]],"date-time":"2008-05-29T20:54:44Z","timestamp":1212094484000},"page":"7803-7808","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":335,"title":["A NOD2\u2013NALP1 complex mediates caspase-1-dependent IL-1\u03b2 secretion in response to\n                    <i>Bacillus anthracis<\/i>\n                    infection and muramyl dipeptide"],"prefix":"10.1073","volume":"105","author":[{"given":"Li-Chung","family":"Hsu","sequence":"first","affiliation":[{"name":"Departments of *Pharmacology and Pathology and"},{"name":"Institute of Molecular Medicine, National Taiwan University, Taipei, 10617 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed R.","family":"Ali","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology and Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna","family":"McGillivray","sequence":"additional","affiliation":[{"name":"Pediatric and Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Hui","family":"Tseng","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology and Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Mariathasan","sequence":"additional","affiliation":[{"name":"Molecular Oncology Department, Genentech, Inc., South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Humke","sequence":"additional","affiliation":[{"name":"Molecular Oncology Department, Genentech, Inc., South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Pediatric and Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Powell","sequence":"additional","affiliation":[{"name":"MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge CB1 9NL, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Nizet","sequence":"additional","affiliation":[{"name":"Pediatric and Medicine, and"},{"name":"**Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishva M.","family":"Dixit","sequence":"additional","affiliation":[{"name":"Molecular Oncology Department, Genentech, Inc., South San Francisco, CA 94080;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology and Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,6,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402038"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1997"},{"key":"e_1_3_3_3_2","first-page":"S1","article-title":"The IL-1 family and inflammatory diseases","volume":"20","author":"Dinarello CA","year":"2002","unstructured":"CA Dinarello, The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 20, S1\u201313 (2002).","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/09680519040100040301"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.015"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.10.027"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02664"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04515"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.06.004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200651200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103685"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66582-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.05.004"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2001.01498.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104911"},{"key":"e_1_3_3_17_2","first-page":"107","article-title":"Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells","volume":"232","author":"Ashwood P","year":"2007","unstructured":"P Ashwood, RP Thompson, JJ Powell, Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells. Exp Biol Med 232, 107\u2013117 (2007).","journal-title":"Exp Biol Med"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36554"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.07.009"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1006627"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7535475"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008072200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/416190a"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600175"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf453"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100250200"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.032"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1724"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073163"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737103"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041215"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.12.032"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-007-7068-4"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36591-2"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00108-2"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402194"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.6.3991"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.08.010"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01502-1"},{"key":"e_1_3_3_40_2","first-page":"305","article-title":"NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype","volume":"63","author":"Netea MG","year":"2005","unstructured":"MG Netea, et al., NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype. Neth J Med 63, 305\u2013308 (2005).","journal-title":"Neth J Med"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.02.004"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1949-1953.2006"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0802726105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:57:45Z","timestamp":1649779065000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0802726105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,3]]},"references-count":42,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2008,6,3]]}},"alternative-id":["10.1073\/pnas.0802726105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0802726105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,3]]},"assertion":[{"value":"2008-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}