{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:13:28Z","timestamp":1791242008034,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic>is the most common pathogen associated with otitis media. To examine the role of Toll-like receptor 2 (TLR2) in host defense against<jats:italic>Streptococcus pneumoniae<\/jats:italic>infection in the middle ear, wild-type (WT; C57BL\/6) and TLR2-deficient (TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were inoculated with<jats:italic>Streptococcus pneumoniae<\/jats:italic>(1 \u00d7 10<jats:sup>6<\/jats:sup>CFU) through the tympanic membrane. Nineteen of 37 TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed bacteremia and died within 3 days after the challenge, compared to only 4 of 32 WT mice that died. Of those that survived, more severe hearing loss in the TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice than in the WT mice was indicated by an elevation in auditory-evoked brain stem response thresholds at 3 or 7 days postinoculation. The histological pathology was characterized by effusion and tissue damage in the middle ear, and in the TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice, the outcome of infection became more severe at 7 days. At both 3 and 7 days postchallenge, the TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice had higher blood bacterial titers than the WT mice (<jats:italic>P<\/jats:italic>&lt; 0.05), and typical bacteria were identified in the effusion from both ears of both mouse groups by acridine orange staining. Moreover, by 3 days postchallenge, the mRNA accumulation levels of NF-\u03baB, tumor necrosis factor alpha, interleukin 1\u03b2, MIP1\u03b1, Muc5ac, and Muc5b were significantly lower in the ears of TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice than in WT mice. In summary, TLR2<jats:sup>\u2212\/\u2212<\/jats:sup>mice may produce relatively low levels of proinflammatory cytokines following pneumococcal challenge, thus hindering the clearance of bacteria from the middle ear and leading to sepsis and a high mortality rate. This study provides evidence that TLR2 is important in the molecular pathogenesis and host response to otitis media.<\/jats:p>","DOI":"10.1128\/iai.00204-09","type":"journal-article","created":{"date-parts":[[2009,5,5]],"date-time":"2009-05-05T01:09:45Z","timestamp":1241485785000},"page":"3100-3108","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Role for Toll-Like Receptor 2 in the Immune Response to<i>Streptococcus pneumoniae<\/i>Infection in Mouse Otitis Media"],"prefix":"10.1128","volume":"77","author":[{"given":"Fengchan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Benedict-Alderfer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing Y.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1462-1470.2006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407550101"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/77528"},{"key":"e_1_3_2_6_2","unstructured":"Reference deleted."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63095-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/342845"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2005.05.017"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MLG.0000195290.71090.A1"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206473200"},{"key":"e_1_3_2_12_2","unstructured":"Reference deleted."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00914.x"},{"key":"e_1_3_2_14_2","first-page":"3075","volume":"23","year":"2003","unstructured":"Johnson, K. 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