{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:53:06Z","timestamp":1768873986900,"version":"3.49.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DC000129"],"award-info":[{"award-number":["DC000129"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DC006279"],"award-info":[{"award-number":["DC006279"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DC012595"],"award-info":[{"award-number":["DC012595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DC014801"],"award-info":[{"award-number":["DC014801"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009012","name":"VA | Veterans Affairs San Diego Healthcare System","doi-asserted-by":"publisher","award":["BX001205"],"award-info":[{"award-number":["BX001205"]}],"id":[{"id":"10.13039\/100009012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009012","name":"VA | Veterans Affairs San Diego Healthcare System","doi-asserted-by":"publisher","award":["RX000977"],"award-info":[{"award-number":["RX000977"]}],"id":[{"id":"10.13039\/100009012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of<jats:italic>ccl3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice to nontypeable<jats:named-content content-type=\"genus-species\">Haemophilus influenzae<\/jats:named-content>(NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced in<jats:italic>ccl3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by an<jats:italic>in vitro<\/jats:italic>assay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline.<jats:italic>ccl3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads in<jats:italic>ccl3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease.<\/jats:p>","DOI":"10.1128\/iai.00148-17","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:30:22Z","timestamp":1503966622000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Otitis Media and Nasopharyngeal Colonization in<i>ccl3<\/i><sup>\u2212\/\u2212<\/sup>Mice"],"prefix":"10.1128","volume":"85","author":[{"given":"Dominik","family":"Deniffel","sequence":"first","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"Ortenau Hospital Offenburg Department of Radiology, Offenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Nuyen","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"Veterans Administration San Diego Healthcare System, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang","family":"Pak","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"Veterans Administration San Diego Healthcare System, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keigo","family":"Suzukawa","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"University of Tokyo Department of Otolaryngology, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"Veterans Administration San Diego Healthcare System, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arwa","family":"Kurabi","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen I.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Medicine\/Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen F.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Otolaryngology, University of California, San Diego, La Jolla, California, USA"},{"name":"Veterans Administration San Diego Healthcare System, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/509332"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31828d9acc"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/516477"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2012.12.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/525856"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199604000-00002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00271-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151236098"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.083001.084359"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1475-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075213"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901167"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/593213"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753425909103170"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-0524"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3342\/ceo.2008.1.4.189"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.3.909"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199802123380706"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.10.019"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2009.06.252"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1189\/jlb.72.6.1190","article-title":"An essential role of macrophage inflammatory protein 1alpha\/CCL3 on the expression of host's innate immunities against infectious complications","volume":"72","author":"Takahashi H","year":"2002","unstructured":"Takahashi H Tashiro T Miyazaki M Kobayashi M Pollard RB Suzuki F . 2002. An essential role of macrophage inflammatory protein 1alpha\/CCL3 on the expression of host's innate immunities against infectious complications. J Leukoc Biol72:1190\u20131197.","journal-title":"J Leukoc Biol"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0404237"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100082"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6364-6369.2001"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700701"},{"key":"e_1_3_3_28_2","unstructured":"Janeway CA Jr Travers P Walport M Shlomchik. 2001. Immunobiology: the immune system in health and disease 5th ed.Garland Science New York NY. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK27122\/."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7667639"},{"key":"e_1_3_3_30_2","unstructured":"Lu P Li L Wu Y Mukaida N Zhang X . 2008. Essential contribution of CCL3 to alkali-induced corneal neovascularization by regulating vascular endothelial growth factor production by macrophages. Mol Vis14:1614\u20131622. http:\/\/www.molvis.org\/molvis\/v14\/a191."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066106"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0265OC"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.12.030"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.8072"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425426"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101043440102"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00938-7"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1163"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016489409126058"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0463.2003.1111012.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.07.026"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki443"},{"key":"e_1_3_3_43_2","volume-title":"Manual of clinical microbiology","author":"Murray PR","year":"1995","unstructured":"Murray PR Baron EJ Pfaller MA Tenover FC Yolken RH (ed). 1995. Manual of clinical microbiology, 7th ed.ASM Press, Washington, DC.","edition":"7"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00148-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00148-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:36:41Z","timestamp":1692952601000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00148-17"}},"subtitle":[],"editor":[{"given":"Shelley M.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1128\/IAI.00148-17"],"URL":"https:\/\/doi.org\/10.1128\/iai.00148-17","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"2017-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00148-17"}}