{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:05:40Z","timestamp":1792069540678,"version":"4.4.0"},"reference-count":91,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":70,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI124349,U19AI162568,UL1TR001866"],"award-info":[{"award-number":["R01AI124349,U19AI162568,UL1TR001866"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["FDN-143332"],"award-info":[{"award-number":["FDN-143332"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Natural resistance to Mycobacterium tuberculosis (\n                      <jats:italic>Mtb<\/jats:italic>\n                      ) infection in some people with HIV (PWH) is unexplained.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb, for 7 PWH who were tuberculin skin test (TST) and IFN-\u03b3 release assay (IGRA) positive (called LTBI) and 6 who were persistently TST and IGRA negative (called resisters).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Alveolar macrophages (AM) from resisters displayed a baseline M1 macrophage phenotype while AM from LTBI did not. Resisters displayed alveolar lymphocytosis, with enrichment of all T cell subpopulations including IFNG-expressing cells. In both groups, mycobactericidal granulysin was expressed almost exclusively by a T cell subtype that coexpressed granzyme B, perforin and NK cell receptors. These poly-cytotoxic T lymphocytes (poly-CTL) overexpressed activating NK cell receptors and were increased in resister BAL. Following challenge with\n                      <jats:italic>Mtb<\/jats:italic>\n                      , only intraepithelial lymphocyte-like cells from LTBI participants responded with increased transcription of IFNG. AM from resisters responded with a stronger TNF signature at 6 hours after infection while at 24 hours after infection, AM from LTBI displayed a stronger IFN-\u03b3 signature. Conversely, at 24 hours after infection, only AM from resisters displayed an upregulation of MHC class I polypeptide\u2013related sequence A (MICA) transcripts, which encode an activating ligand for poly-CTL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These results suggest that poly-CTL and M1-like pre-activated AM mediate the resister phenotype in PWH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>National Institutes of Health. Canadian Institutes of Health Research. Digital Research Alliance of Canada. French National Research Agency. French National Agency for Research on AIDS and Viral Hepatitis. St. Giles Foundation. General Atlantic Foundation. South African Medical Research Council Centre for Tuberculosis Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci188016","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T12:00:38Z","timestamp":1737460838000},"source":"Crossref","is-referenced-by-count":31,"title":["Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli"],"prefix":"10.1172","volume":"135","author":[{"given":"Monica","family":"Dallmann-Sauer","sequence":"first","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, Canada."},{"name":"McGill International TB Centre, and"},{"name":"Departments of Human Genetics and Medicine, Faculty of Medicine and Health Science, McGill University, Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-1713","authenticated-orcid":true,"given":"Vinicius M.","family":"Fava","sequence":"additional","affiliation":[{"name":"Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, Canada."},{"name":"McGill International TB Centre, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanus T.","family":"Malherbe","sequence":"additional","affiliation":[{"name":"South African Medical Research Council Centre for Tuberculosis Research; 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