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Here we interrogated the airway immune response at single-cell resolution in bronchoalveolar lavage from positron emission and computed tomography-characterized recent TB household contacts, who either controlled the infection or progressed to TB disease, as well as of patients with active TB at diagnosis. Single-cell RNA sequencing revealed type I IFN-dependent and IFN-independent neutrophil signatures in bronchoalveolar lavage from patients with active TB and TB progressors. We report an inverse relationship between airway neutrophils and T cells, with T cells showing signatures of exhaustion, cytotoxicity and cell death in progressors and patients with active TB with a neutrophil-dominated airway profile. Conversely, we identified T cell signatures of protection in nonprogressor contacts dominated by genes related to regulation, quiescence and a stem-like profile. Our findings from early human airway responses in TB contacts reveal genes, pathways and cell states that may dictate infection outcome and inform strategies for developing effective host-directed therapies and vaccines.\n                  <\/jats:p>","DOI":"10.1038\/s41590-026-02544-0","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T09:02:28Z","timestamp":1782291748000},"page":"1577-1589","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-4857","authenticated-orcid":false,"given":"William J.","family":"Branchett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee-Whang","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Probir","family":"Chakravarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Novsarka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-8477","authenticated-orcid":false,"given":"Hubert","family":"Slawinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-2040","authenticated-orcid":false,"given":"Katalin A.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2753-1800","authenticated-orcid":false,"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anver","family":"Kamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-5421","authenticated-orcid":false,"given":"Pranabashis","family":"Haldar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-6134","authenticated-orcid":false,"given":"Anne","family":"O\u2019Garra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"2544_CR1","unstructured":"Global Tuberculosis Report 2025 (WHO, 2025)."},{"key":"2544_CR2","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/s41564-024-01683-0","volume":"9","author":"MA Behr","year":"2024","unstructured":"Behr, M. 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