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Using C57BL\/6 and CBA\/J inbred mice, we previously identified three chromosomal regions associated with<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>susceptibility (<jats:italic>Cnes1<\/jats:italic>,<jats:italic>Cnes2<\/jats:italic>, and<jats:italic>Cnes3<\/jats:italic>). To validate and characterize the role of<jats:italic>Cnes2<\/jats:italic>during the host response, we constructed a congenic strain on the C57BL\/6 background (B6.CBA-<jats:italic>Cnes2<\/jats:italic>). Phenotypic analysis of B6.CBA-<jats:italic>Cnes2<\/jats:italic>mice 35 days after<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-\u03b3) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL\/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b<jats:sup>+<\/jats:sup>dendritic cells, and CD4<jats:sup>+<\/jats:sup>cells in B6.CBA-<jats:italic>Cnes2<\/jats:italic>than in C57BL\/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-<jats:italic>Cnes2<\/jats:italic>mice. Taken together, these findings demonstrate that the<jats:italic>Cnes2<\/jats:italic>interval is a potent regulator of host defense, immune responsiveness, and differential Th1\/Th2 polarization following<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>infection.<\/jats:p>","DOI":"10.1128\/iai.00697-15","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T02:08:54Z","timestamp":1442282934000},"page":"4541-4554","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["The<i>Cnes2<\/i>Locus on Mouse Chromosome 17 Regulates Host Defense against Cryptococcal Infection through Pleiotropic Effects on Host Immunity"],"prefix":"10.1128","volume":"83","author":[{"given":"Mitra","family":"Shourian","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Critical Care and Research Institute of the McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Flaczyk","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Critical Care and Research Institute of the McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Angers","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Critical Care and Research Institute of the McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara C.","family":"Mindt","sequence":"additional","affiliation":[{"name":"Complex Traits Group, Department of Microbiology and Immunology, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg H.","family":"Fritz","sequence":"additional","affiliation":[{"name":"Complex Traits Group, Department of Microbiology and Immunology, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1447-1247","authenticated-orcid":false,"given":"Salman T.","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Department of Medicine and Division of Experimental Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Critical Care and Research Institute of the McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2522"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.4.515"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200907-063AL"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043582"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060431"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056269"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780701390140"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042439"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir152"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00573-13"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.29.2.494-499.1980"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/00362178585380331"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.47.1.282-287.1985"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.4049\/jimmunol.163.7.3907","article-title":"Ig heavy chain complex-linked genes influence the immune response in a murine cryptococcal infection","volume":"163","author":"Lovchik JA","year":"1999","unstructured":"Lovchik JA, Wilder JA, Huffnagle GB, Riblet R, Lyons CR, Lipscomb MF. 1999. 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