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The intravenous bolus injection of <jats:italic>S. mansoni<\/jats:italic> eggs into <jats:italic>S. mansoni<\/jats:italic>\u2010sensitized TLR3<jats:sup>+\/+<\/jats:sup> mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and <jats:italic>ex vivo<\/jats:italic> spleen and lung cultures at day 8 after egg injection. Lungs from TLR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3<jats:sup>+\/+<\/jats:sup> mice. Macrophages from TLR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T cells were present in the lungs of TLR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with TLR3<jats:sup>+\/+<\/jats:sup> mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3<jats:sup>\u2212\/\u2212<\/jats:sup> mice released significantly higher levels of IL\u201017 levels relative to TLR3<jats:sup>+\/+<\/jats:sup> cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2\u2010driven granulomatous response as its absence enhanced immunopathology.<\/jats:p>","DOI":"10.1002\/eji.200838629","type":"journal-article","created":{"date-parts":[[2008,11,13]],"date-time":"2008-11-13T11:08:03Z","timestamp":1226574483000},"page":"3436-3449","source":"Crossref","is-referenced-by-count":26,"title":["TLR3 modulates immunopathology during a <i>Schistosoma mansoni<\/i> egg\u2010driven Th2 response in the lung"],"prefix":"10.1002","volume":"38","author":[{"given":"Amrita D.","family":"Joshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas W.","family":"Lukacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Kunkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory M.","family":"Hogaboam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,11,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100014"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-07"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2005.00765.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.12.6712"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwg052"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwm073"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh246"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri843"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.2.777"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3920"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.566"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20001"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh319"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526273"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200706-067TH"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411223200"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310175200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21273"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1007689"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05746"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0241OC"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.4984"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.1170"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.3885"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/382089"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7454"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000088882"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.12.012"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.09.013"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00732-07"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.019"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.4.2486"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27727"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.078527"},{"key":"e_1_2_6_37_2","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.4049\/jimmunol.158.9.4478","article-title":"Transgene\u2010induced production of IL\u20104 alters the development and collagen expression of T helper cell 1\u2010type pulmonary granulomas","volume":"158","author":"Lukacs N. 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