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Intratibial infection additionally triggered compartment\u2010specific immune responses, including neutrophil and macrophage expansion, transient B\u2010cell depletion, and activation of interferon\u2010\u03b3\n                      <jats:sup>+<\/jats:sup>\n                      (IFN\u2010\u03b3\n                      <jats:sup>+<\/jats:sup>\n                      ) T cells, reflecting active immune remodeling at the infection site. Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation. Compared to intratibial infection, intracardiac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This\n                      <jats:italic>M. smegmatis<\/jats:italic>\n                      \u2013based murine model provides a straightforward, reliable, and immunopathologically relevant platform for exploring host\u2013pathogen dynamics, immune\u2010driven bone destruction, and early\u2010stage therapeutic testing in skeletal TB, all within standard BSL\u20101 laboratories. This model fills a critical gap by enabling BSL\u20101 research into skeletal TB mechanisms and drug development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70101","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T03:02:40Z","timestamp":1767754960000},"page":"5-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Establishment of a biosafe murine model of skeletal tuberculosis using\n                    <i>Mycobacterium smegmatis<\/i>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5447-973X","authenticated-orcid":false,"given":"Yewei","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhuai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"},{"name":"Center of Research Excellence in Allergy &amp; Immunology, Research Department Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiulin","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathachit","family":"Limjunyawong","sequence":"additional","affiliation":[{"name":"Center of Research Excellence in Allergy &amp; Immunology, Research Department Faculty of Medicine Siriraj Hospital, Mahidol University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Southwest Hospital, Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"WHO Consolidated Guidelines on Tuberculosis. 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