{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:59:49Z","timestamp":1790495989637,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1670,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N023706\/1"],"award-info":[{"award-number":["MR\/N023706\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clearance of intracellular infections caused by Salmonella Typhimurium (STm) requires IFN-\u03b3 and the Th1-associated transcription factor T-bet. Nevertheless, whereas IFN-\u03b3\u2212\/\u2212 mice succumb rapidly to STm infections, T-bet\u2212\/\u2212 mice do not. In this study, we assess the anatomy of immune responses and the relationship with bacterial localization in the spleens and livers of STm-infected IFN-\u03b3\u2212\/\u2212 and T-bet\u2212\/\u2212 mice. In IFN-\u03b3\u2212\/\u2212 mice, there is deficient granuloma formation and inducible NO synthase (iNOS) induction, increased dissemination of bacteria throughout the organs, and rapid death. The provision of a source of IFN-\u03b3 reverses this, coincident with subsequent granuloma formation and substantially extends survival when compared with mice deficient in all sources of IFN-\u03b3. T-bet\u2212\/\u2212 mice induce significant levels of IFN-\u03b3\u2212 after challenge. Moreover, T-bet\u2212\/\u2212 mice have augmented IL-17 and neutrophil numbers, and neutralizing IL-17 reduces the neutrophilia but does not affect numbers of bacteria detected. Surprisingly, T-bet\u2212\/\u2212 mice exhibit surprisingly wild-type\u2013like immune cell organization postinfection, including extensive iNOS+ granuloma formation. In wild-type mice, most bacteria are within iNOS+ granulomas, but in T-bet\u2212\/\u2212 mice, most bacteria are outside these sites. Therefore, Th1 cells act to restrict bacteria within IFN-\u03b3\u2013dependent iNOS+ granulomas and prevent dissemination.<\/jats:p>","DOI":"10.4049\/jimmunol.2000089","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T22:41:25Z","timestamp":1593211285000},"page":"708-719","source":"Crossref","is-referenced-by-count":15,"title":["Mice Deficient in T-bet Form Inducible NO Synthase\u2013Positive Granulomas That Fail to Constrain <i>Salmonella<\/i>"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-255X","authenticated-orcid":false,"given":"Marisol","family":"Perez-Toledo","sequence":"first","affiliation":[{"name":"Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT ,","place":["United 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