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Human transgenic CD46 homozygous mice (CD46<jats:sup>+\/+<\/jats:sup>) are prone to lethal sepsis upon infection with <jats:italic>Neisseria meningitidis (N. meningitidis)<\/jats:italic>. However, the underlying mechanisms are poorly understood. Here, we determined thatCD46<jats:sup>+\/+<\/jats:sup> mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro\u2010inflammatory mediators such as IL\u20106, TNF, IL\u201012, and IL\u20101\u03b2 In the presence of M\u2010CSF or GM\u2010CSF, CD46 signaling enhances monocyte\u2010macrophage differentiation. Additionally, CD46<jats:sup>+\/+<\/jats:sup> macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46<jats:sup>+\/+<\/jats:sup> peritoneal macrophages aggravated septic responses in wild\u2010type mice, but the depletion of macrophages partially alleviated septic reactions in CD46<jats:sup>+\/+<\/jats:sup> mice after <jats:italic>N. meningitidis<\/jats:italic> infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages.<\/jats:p>","DOI":"10.1002\/eji.201646397","type":"journal-article","created":{"date-parts":[[2016,10,29]],"date-time":"2016-10-29T02:52:45Z","timestamp":1477709565000},"page":"119-130","source":"Crossref","is-referenced-by-count":19,"title":["CD46 accelerates macrophage\u2010mediated host susceptibility to meningococcal sepsis in a murine model"],"prefix":"10.1002","volume":"47","author":[{"given":"Xiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, the Wenner\u2010Gren Institute Stockholm University  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine Shanxi Agricultural University  Taigu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Sj\u00f6linder","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, the Wenner\u2010Gren Institute Stockholm University  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, the Wenner\u2010Gren Institute Stockholm University  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Sj\u00f6linder","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, the Wenner\u2010Gren Institute Stockholm University  Stockholm Sweden"},{"name":"Cancer Center M\u00e4lar Hospital  Eskilstuna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc1876"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784980572"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445174"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.359562"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-014-0029-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.3733"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445427"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59643"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143593"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc14124"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.6298"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80071-L"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4992-4999.2003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01732-07"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.03.012"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00095.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.4.2543"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00257"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.05.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086476"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.433"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.3072-3082.2005"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324259"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1917"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1128\/JVI.73.6.4776-4785.1999","article-title":"Human CD46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of gamma interferon: dependence on the CD46 cytoplasmic domains","volume":"73","author":"Hirano A.","year":"1999","journal-title":"J. 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