{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:05Z","timestamp":1792788605369,"version":"4.5.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["CDF1576"],"award-info":[{"award-number":["CDF1576"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South African National Research Foundation","award":["SARChI TB Biomarkers #86535"],"award-info":[{"award-number":["SARChI TB Biomarkers #86535"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP37772; OPP1055806; OPP51919"],"award-info":[{"award-number":["OPP37772; OPP1055806; OPP51919"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South African National Research Foundation","award":["CSUR60502163639"],"award-info":[{"award-number":["CSUR60502163639"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["UK Medical Research Council"],"award-info":[{"award-number":["UK Medical Research Council"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tb<\/jats:italic>\n                    ) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>tb<\/jats:italic>\n                    infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13\u201318 months, 742 at 7\u201312 months and 5,131 detected 1\u20136 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1\u20136 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0278295","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T14:37:09Z","timestamp":1669905429000},"page":"e0278295","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis"],"prefix":"10.1371","volume":"17","author":[{"given":"Stuart","family":"Meier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Seddon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizna","family":"Maasdorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9anie","family":"Kleynhans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelita","family":"du Plessis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre G.","family":"Loxton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanus T.","family":"Malherbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Zak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergal J.","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H. 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