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This study employed high-dimensional mass cytometry (CyTOF) within the splenic compartment and serum lipidomics to map the integrated immuno-metabolic landscape in BCG-vaccinated and non-vaccinated mice following infection with the H37Rv strain. We report that BCG vaccination was associated with a distinct phenotype characterised by the priming of antimicrobial myeloid subsets (CD11b+ Mac2+\/Mac3+) and lipidomic pathways away from stress-induced inflammatory responses. In contrast, non-vaccinated hosts exhibited a dysregulated response, characterised by a systemic cortisol surge, a lipidomic profile suggestive of reduced bioactive lipids (including PPAR\u03b3 ligands such as 13-HODE and 19,20-DiHDPA), and the reactive mobilisation of CD103\u2009+\u2009CD4+\/CD8\u2009+\u2009T cells and activated B cell subsets to the spleen. These findings reveal that protection is not solely cellular but relies on a stable metabolic environment that supports immune function. While infection in naive hosts drives a resource-depleting stress response that likely compromises macrophage efficacy, BCG vaccination establishes an integrated multiparametric defence, preventing pathogen-driven metabolic manipulation and maintaining the necessary lipid mediators for effective inflammation resolution and bacterial control.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-58623-7","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:37:33Z","timestamp":1782488253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive CyTOF and lipidomic analysis of splenic immune and serum lipid responses to BCG vaccination and H37Rv challenge in BALB\/c mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Matthieu","family":"Van-Tilbeurgh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto Marcos","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Gallou\u00ebt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Dagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Goulding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Keeble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Mei","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger Le","family":"Grand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagwati","family":"Khatri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"58623_CR1","unstructured":"WHO. 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