{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:09Z","timestamp":1785432489532,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018684","name":"National Health Commission of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["2024ZD0529300"],"award-info":[{"award-number":["2024ZD0529300"]}],"id":[{"id":"10.13039\/501100018684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["25SF1901200"],"award-info":[{"award-number":["25SF1901200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}],"id":[{"id":"https:\/\/ror.org\/03kt66j61","id-type":"ROR","asserted-by":"publisher"}]},{"award":["25SF1901200"],"award-info":[{"award-number":["25SF1901200"]}],"id":[{"id":"https:\/\/ror.org\/03kt66j61","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC 12024115"],"award-info":[{"award-number":["SHDC 12024115"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SHDC 12024115"],"award-info":[{"award-number":["SHDC 12024115"]}],"id":[{"id":"https:\/\/ror.org\/02zrtve16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: In some children with immunodeficiency, Bacille Calmette\u2013Gu\u00e9rin (BCG) vaccination can lead to dissemination and severe infection, including severe intracranial infection, called disseminated BCG disease (BCGosis), which is characterized by high rates of disability and mortality. However, the specific routes by which BCG crosses CNS barriers and the patterns of temporal remodeling of the CNS immune microenvironment during infection have yet to be fully elucidated. Methods: Mice were infected with BCG through tail vein injection to construct an intracerebral mycobacterial infection mouse model, wherein the brain was collected and analyzed using single-cell RNA sequencing. We profiled temporal transcriptomic changes in cell populations, pathways, and cell\u2013cell communication associated with anti-mycobacterial activity and inflammation-induced disturbance of physiological brain activities. Results: After BCG was injected via tail vein, histopathological images and cultured colonies of brain tissue confirmed successful brain infection. Then, whole-brain tissue was dissected for 10\u00d7 Genomics single-cell sequencing, and we acquired 15 cell types. Dysfunction and inflammatory responses were observed in endothelial and ependymal cells. Infection induced dynamic state transitions in microglia, enabling their differentiation into disease-related and interferon-responsive states. Along with peripheral immune cells, microglia formed temporally structured communication networks that mediated early events such as chemokine recruitment and inflammatory storms, and facilitated late-stage immune checkpoint upregulation. Conclusions: This study proposes BCSFB as a possible pathway of mycobacteria invasion and reveals the temporality of immune response processes in the pathogenesis of intracerebral mycobacterial infection.<\/jats:p>","DOI":"10.3390\/pathogens15050531","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:17:23Z","timestamp":1779203843000},"page":"531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporally Resolved Single-Cell RNA Sequencing Reveals Pathogenesis and Immune Responses in Intracerebral Bacille Calmette\u2013Gu\u00e9rin (BCG) Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Shiqi","family":"Xie","sequence":"first","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4507-7212","authenticated-orcid":false,"given":"Huiling","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqiong","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, 130 Dong An Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5584-8963","authenticated-orcid":false,"given":"Yang","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-3559","authenticated-orcid":false,"given":"Xiao-Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, 130 Dong An Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-4389","authenticated-orcid":false,"given":"Zhidong","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-7352","authenticated-orcid":false,"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Public Health Clinical Center, Fudan University, 2901 Cao Lang Road, Jinshan District, Shanghai 201508, China"},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, 130 Dong An Road, Xuhui District, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","article-title":"Effect of BCG Vaccination on Childhood Tuberculous Meningitis and Miliary Tuberculosis Worldwide: A Meta-Analysis and Assessment of Cost-Effectiveness","volume":"367","author":"Trunz","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/cid\/cit790","article-title":"Protection by BCG Vaccine against Tuberculosis: A Systematic Review of Randomized Controlled Trials","volume":"58","author":"Mangtani","year":"2014","journal-title":"Clin. 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