{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:40:55Z","timestamp":1791726055941,"version":"4.3.4"},"reference-count":39,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Crick African Network"},{"DOI":"10.13039\/100010438","name":"Francis Crick Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"crossref","award":["SANRF86535"],"award-info":[{"award-number":["SANRF86535"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Tuberculosis (TB) is characterized by the formation of heterogeneous, immune-rich granulomas in the lungs. Host and pathogen factors contribute to this heterogeneity, but the molecular and cellular drivers of granuloma diversity remain inadequately understood owing to limitations in experimental techniques. In this study, we developed an approach that combines passive CLARITY (PACT)-based clearing with light-sheet fluorescence microscopy to visualize lesion architecture and lung involvement in Mycobacterium tuberculosis-infected C3HeB\/FeJ mice. Three-dimensional rendering of post-mortem lungs revealed critical architectural features in lesion development that traditional thin-section imaging could not detect. Wild-type M. tuberculosis infection resulted in organized granulomas, with median sizes increasing to 3.74\u00d7108\u00a0\u00b5m3 and occupying \u223c10% of the total lung volume by day 70 post-infection. In contrast, infection with the avirulent ESX-1 deletion mutant strain resulted in diffuse and sparsely organized CD11b recruitment (median size of 8.22\u00d7107\u00a0\u00b5m3), primarily located in the lung periphery and minimally involving the airways (0.23% of the total lung space). Additionally, we present a method for volumetric correlative light and electron microscopy, enabling tracking of individual immune cell populations within granulomas.<\/jats:p>","DOI":"10.1242\/dmm.052185","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T03:21:29Z","timestamp":1742959289000},"source":"Crossref","is-referenced-by-count":4,"title":["Correlative 3D imaging method for analysing lesion architecture in susceptible mice infected with <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5208-0506","authenticated-orcid":false,"given":"Caroline G. G.","family":"Beltran","sequence":"first","affiliation":[{"name":"Stellenbosch University 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]},{"name":"South African Medical Research Council Centre for Tuberculosis Research 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]},{"name":"Stellenbosch University 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7558-7916","authenticated-orcid":false,"given":"Jurgen","family":"Kriel","sequence":"additional","affiliation":[{"name":"Central Analytical Facilities 3 , Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]},{"name":"Stellenbosch University 3 , Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Botha","sequence":"additional","affiliation":[{"name":"Stellenbosch University 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]},{"name":"South African Medical Research Council Centre for Tuberculosis Research 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]},{"name":"Stellenbosch University 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret B.","family":"Nolan","sequence":"additional","affiliation":[{"name":"Stellenbosch University 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]},{"name":"South African Medical Research Council Centre for Tuberculosis Research 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]},{"name":"Stellenbosch University 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute 4 , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Loos","sequence":"additional","affiliation":[{"name":"Stellenbosch University 5 Department of Physiological Sciences , , Stellenbosch 7602 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano G.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute 4 , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Walzl","sequence":"additional","affiliation":[{"name":"Stellenbosch University 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , , Cape Town 7505 ,","place":["South Africa"]},{"name":"South African Medical Research Council Centre for Tuberculosis Research 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]},{"name":"Stellenbosch University 2 , Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences , , Cape Town 7501 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"2025101110565233100_DMM052185C1","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. 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