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Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined <jats:italic>in vivo<\/jats:italic> the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV\u2010A59 serotype. To address this, C57BL\/6 (wild\u2010type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV\u2010A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV\u2010A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3\u2010induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon\u2010<jats:italic>\u03b2<\/jats:italic>, interleukin\u20106, tumour necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic>, CXCL1, CCL2, CXCL10 and alarmin (interleukin\u201033) than in MHV\u2010A59\u2010infected WT mice and in MHV3\u2010infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3\u2010infected WT mice whereas they were sustained in MHV\u2010A59\u2010infected WT mice and MHV3\u2010infected TLR2 KO. MHV3 <jats:italic>in vitro<\/jats:italic> infection of macrophagic cells induced rapid and higher viral replication and\/or interleukin\u20106 induction in comparison to MHV\u2010A59, and depended on viral activation of TLR2 and p38 mitogen\u2010activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3\u2010induced acute fulminant hepatitis.<\/jats:p>","DOI":"10.1111\/imm.12627","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T15:50:42Z","timestamp":1465314642000},"page":"204-224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Toll\u2010like receptor\u20102 exacerbates murine acute viral hepatitis"],"prefix":"10.1111","volume":"149","author":[{"given":"Christian","family":"Bleau","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Burnette","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aveline","family":"Filliol","sequence":"additional","affiliation":[{"name":"U.1085 Inserm IRSET Institute of Research in Environmental and Occupational Health Universit\u00e9 de Rennes 1 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Piquet\u2010Pellorce","sequence":"additional","affiliation":[{"name":"U.1085 Inserm IRSET Institute of Research in Environmental and Occupational Health Universit\u00e9 de Rennes 1 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Samson","sequence":"additional","affiliation":[{"name":"U.1085 Inserm IRSET Institute of Research in Environmental and Occupational Health Universit\u00e9 de Rennes 1 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Lamontagne","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110065"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-012-0247-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.08.067"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000226136"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.156307"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/421780"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02595.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041153"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir522"},{"key":"e_1_2_9_11_1","first-page":"7315","article-title":"Toll\u2010like receptor 2 promotes T helper 17 cells response in hepatitis B virus infection","volume":"8","author":"Zhao RR","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2009.01.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308057100"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12658-12666.2005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7094"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03079.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-006-0082-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2010.01390.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1573"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399401002812"},{"key":"e_1_2_9_21_1","first-page":"107","article-title":"Physiology and pathophysiology of liver inflammation, damage and repair","volume":"59","author":"Ramadori G","year":"2008","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385885-6.00009-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4049\/jimmunol.114.1_Part_1.221","article-title":"Immunopathology of mouse hepatitis virus type 3 infection. 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