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We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination. Our findings reveal that high-dose intravenous BCG induces an influx of polyfunctional T cells and macrophages in the airways, with alveolar macrophages from high-dose intravenous BCG displaying a basal activation state in the absence of purified protein derivative stimulation, defined in part by interferon signaling. Enhanced intercellular immune signaling and stronger T helper 1\u2013T helper 17 transcriptional responses were observed following purified protein derivative stimulation. These results suggest that high-dose intravenous BCG vaccination creates a specialized immune environment that primes airway cells for effective\n            <jats:italic>Mtb<\/jats:italic>\n            clearance.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adq8229","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T19:03:34Z","timestamp":1735758214000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-6706","authenticated-orcid":true,"given":"Joshua M.","family":"Peters","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, MIT, Cambridge, MA, USA."},{"name":"Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Irvine","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA, USA."},{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. 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