{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:26:36Z","timestamp":1769059596083,"version":"3.49.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Salmonella enterica is a ubiquitous Gram-negative intracellular bacterium that continues to pose a global challenge to human health. The etiology of Salmonella pathogenesis is complex and controlled by pathogen, environmental, and host genetic factors. In fact, patients immunodeficient in genes in the IL-12, IL-23\/IFN-\u03b3 pathway are predisposed to invasive nontyphoidal Salmonella infection. Using a forward genomics approach by N-ethyl-N-nitrosourea (ENU) germline mutagenesis in mice, we identified the Ity14 (Immunity to Typhimurium locus 14) pedigree exhibiting increased susceptibility following in vivo Salmonella challenge. A DNA-binding domain mutation (p.G418_E445) in Stat4 (Signal Transducer and Activator of Transcription Factor 4) was the causative mutation. STAT4 signals downstream of IL-12 to mediate transcriptional regulation of inflammatory immune responses. In mutant Ity14 mice, the increased splenic and hepatic bacterial load resulted from an intrinsic defect in innate cell function, IFN-\u03b3\u2013mediated immunity, and disorganized granuloma formation. We further show that NK and NKT cells play an important role in mediating control of Salmonella in Stat4Ity14\/Ity14 mice. Stat4Ity14\/Ity14 mice had increased expression of genes involved in cell\u2013cell interactions and communication, as well as increased CD11b expression on a subset of splenic myeloid dendritic cells, resulting in compromised recruitment of inflammatory cells to the spleen during Salmonella infection. Stat4Ity14\/Ity14 presented upregulated compensatory mechanisms, although inefficient and ultimately Stat4Ity14\/Ity14 mice develop fatal bacteremia. The following study further elucidates the pathophysiological impact of STAT4 during Salmonella infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1301370","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T05:07:34Z","timestamp":1385615254000},"page":"259-270","source":"Crossref","is-referenced-by-count":18,"title":["Altered IFN-\u03b3\u2013Mediated Immunity and Transcriptional Expression Patterns in <i>N<\/i>-Ethyl-<i>N<\/i>-Nitrosourea\u2013Induced STAT4 Mutants Confer Susceptibility to Acute Typhoid-like Disease"],"prefix":"10.1093","volume":"192","author":[{"given":"Megan M","family":"Eva","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko E","family":"Yuki","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shauna M","family":"Dauphinee","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy A","family":"Schwartzentruber","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"McGill University and Genome Quebec Innovation Centre , Montreal, Quebec H3B 1S6,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Pyzik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maril\u00e8ne","family":"Paquet","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Pathologie et de Microbiologie, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al , Saint-Hyacinthe, Quebec J2S 5B5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Lathrop","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"McGill University and Genome Quebec Innovation Centre , Montreal, Quebec H3B 1S6,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"McGill University and Genome Quebec Innovation Centre , Montreal, Quebec H3B 1S6,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia M","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Department of Medicine, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Malo","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Complex Traits Group, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]},{"name":"Department of Medicine, McGill University , Montreal, Quebec H3G 0B1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2025032404051851300_r1","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bull. 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