{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:28:13Z","timestamp":1783074493357,"version":"3.54.6"},"reference-count":52,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T00:00:00Z","timestamp":1567209600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC000129"],"award-info":[{"award-number":["DC000129"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC006279"],"award-info":[{"award-number":["DC006279"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC012595"],"award-info":[{"award-number":["DC012595"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC014801"],"award-info":[{"award-number":["DC014801"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Pathogen recognition following infection in mammals depends mainly on TLRs and NLRs. Herein, we evaluate the role of NOD1 and NOD2 signaling in the inflammatory responses of the middle ear (ME) mucosa and leukocytes recruitment to infection site during otitis media (OM). OM is a common pediatric disease with prevalent repercussions on hearing health. While many risk factors have been implicated to OM proneness, immunity and the triggering of inflammation are central to OM pathology. We observed that many genes encoding members of the NOD leucine-rich repeat and their downstream adaptor\/effector molecules were strongly regulated during the course of OM. When compared to wild type C57BL\/6 mice, NOD1- and NOD2-deficient mice were susceptible to prolonged OM infection by non-typeable Haemophilus influenza. NOD1-deficient mice appeared to have reduced macrophage enlistment with a delayed inflammatory response by neutrophils and prolonged mucosal hyperplasia, whereas NOD2 knockouts exhibited an overall reduction in the number of leukocytes recruited to the ME, leading to delayed bacterial clearance. Altogether, these data show that the NODs play a role in the pathogenesis and recovery of OM and reinforce the importance of innate immune signaling in the protective host response.<\/jats:p>","DOI":"10.1177\/1753425919872266","type":"journal-article","created":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T06:48:23Z","timestamp":1567234103000},"page":"503-512","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["NOD1\/NOD2-mediated recognition of non-typeable\n                    <i>Haemophilus influenzae<\/i>\n                    activates innate immunity during otitis media"],"prefix":"10.1177","volume":"25","author":[{"given":"Jasmine","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Leichtle","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"},{"name":"Department of Otolaryngology, University of L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Zuckerman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang","family":"Pak","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"},{"name":"San Diego Veterans Administration Healthcare System, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Spriggs","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-9496","authenticated-orcid":false,"given":"Arwa","family":"Kurabi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, USA"},{"name":"San Diego Veterans Administration Healthcare System, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,8,31]]},"reference":[{"key":"bibr1-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.3.514"},{"key":"bibr2-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24190"},{"key":"bibr3-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00271-1"},{"key":"bibr4-1753425919872266","volume-title":"Evidence-based otitis media","author":"Rosenfeld R","year":"2003","edition":"2"},{"key":"bibr5-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/160.1.83"},{"key":"bibr6-1753425919872266","doi-asserted-by":"publisher","DOI":"10.3109\/00016489609137827"},{"key":"bibr7-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2018.08.004"},{"key":"bibr8-1753425919872266","unstructured":"World Health Organization. Chronic suppurative otitis media: burden of illness and management options, www.who.int\/pbd\/deafness\/activities\/hearing_care\/otitis_media.pdf (2004, accessed 29 January 2019)."},{"key":"bibr9-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1177\/0194599816643510"},{"key":"bibr10-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.63"},{"key":"bibr11-1753425919872266","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/INF.0b013e31828d9acc","volume":"32","author":"Casey JR","year":"2013","journal-title":"Pediatr infect Dis J"},{"key":"bibr12-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199604000-00002"},{"key":"bibr13-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu714"},{"key":"bibr14-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00100-06"},{"key":"bibr15-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2011.03.009"},{"key":"bibr16-1753425919872266","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1651-2227.2009.01506.x","volume":"99","author":"H\u00e5berg SE","year":"2010","journal-title":"Acta Paediatr"},{"key":"bibr17-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1177\/000348949310200711"},{"key":"bibr18-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-010-0158-3"},{"key":"bibr19-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1086\/593213"},{"key":"bibr20-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1177\/1753425909103170"},{"key":"bibr21-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1042\/BST0351479"},{"key":"bibr22-1753425919872266","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00327"},{"key":"bibr23-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606242200"},{"key":"bibr24-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092239"},{"key":"bibr25-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008072200"},{"key":"bibr26-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi135"},{"key":"bibr27-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.032805"},{"key":"bibr28-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2010.09.026"},{"key":"bibr29-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2011.06.006"},{"key":"bibr30-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090933"},{"key":"bibr31-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0463.2003.1111012.x"},{"key":"bibr32-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.07.026"},{"key":"bibr33-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/158.6.1309"},{"key":"bibr34-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1475-7"},{"key":"bibr35-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki443"},{"key":"bibr36-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-11-94"},{"key":"bibr37-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2009.03.012"},{"key":"bibr38-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007355"},{"key":"bibr39-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1139\/y06-076"},{"key":"bibr40-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01404.x"},{"key":"bibr41-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0375TR"},{"key":"bibr42-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02527.x"},{"key":"bibr43-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2011.02069.x"},{"key":"bibr44-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-015-0859-0"},{"key":"bibr45-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-018-3335-4"},{"key":"bibr46-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0411183"},{"key":"bibr47-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/408169"},{"key":"bibr48-1753425919872266","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01483"},{"key":"bibr49-1753425919872266","first-page":"545","volume":"118","author":"Watanabe T","year":"2008","journal-title":"J Clin Invest"},{"key":"bibr50-1753425919872266","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.4340"},{"key":"bibr51-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.08.022"},{"key":"bibr52-1753425919872266","doi-asserted-by":"publisher","DOI":"10.1021\/jm300503b"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425919872266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1753425919872266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425919872266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:02:56Z","timestamp":1777460576000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1753425919872266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,31]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1177\/1753425919872266"],"URL":"https:\/\/doi.org\/10.1177\/1753425919872266","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,31]]}}}