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In this study, we investigated the effects of TS on immune responses and its role in exacerbating Mycobacterium tuberculosis (Mtb) infection. TS induced anxiety-like behaviors, disrupted hypothalamic\u2013pituitary\u2013adrenal (HPA) axis homeostasis, altered hormone secretion patterns, and led to dysregulation of stress response genes in mice. Single-cell RNA sequencing of the spleen revealed severe immune dysfunction upon TS, characterized by inhibition of Th17 differentiation, IL-17 signaling, and antigen presentation. Importantly, TS affects the crosstalk between the HPA axis and the spleen through ligand\u2013receptor interactions. Furthermore, TS exacerbated the severity of Mtb infection and disturbed infection-induced gene regulation. TS impairs Th1\/Th2 differentiation through neuroendocrine immune dysregulation, and also compromises macrophage immune function, further weakening host defense. These findings could greatly contribute to understanding TS-induced neuroendocrine immune regulation and deteriorated infection.<\/jats:p>","DOI":"10.3390\/ijms27041919","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T09:22:46Z","timestamp":1771320166000},"page":"1919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transport Stress Induces Neuroimmune Dysregulation and Exacerbates Mycobacterium Tuberculosis Infection in Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiaojuan","family":"Gou","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Lei","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Yang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 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