{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:40:00Z","timestamp":1788838800770,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010888","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"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","award":["SAMRC Clinician Researcher M.D PhD Development programme"],"award-info":[{"award-number":["SAMRC Clinician Researcher M.D PhD Development programme"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001713","name":"EDCTP","doi-asserted-by":"crossref","award":["TMA2018CDF-2353-NeutroTB"],"award-info":[{"award-number":["TMA2018CDF-2353-NeutroTB"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["NIH 1R01AI124349"],"award-info":[{"award-number":["NIH 1R01AI124349"]}]},{"name":"NIH","award":["NIH 1R01AI124349"],"award-info":[{"award-number":["NIH 1R01AI124349"]}]},{"name":"NIH","award":["NIH 1R01AI124349"],"award-info":[{"award-number":["NIH 1R01AI124349"]}]},{"DOI":"10.13039\/501100020730","name":"Walter and Eliza Hall Institute of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020730","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil <jats:italic>Mtb<\/jats:italic> infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMN<jats:sub>HITTIN<\/jats:sub>) and 11 HIT (PMN<jats:sub>HIT<\/jats:sub>) were isolated and infected with <jats:italic>Mtb<\/jats:italic> H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMN<jats:sub>HITTIN<\/jats:sub> and PMN<jats:sub>HIT<\/jats:sub>, we focused on the 6h timepoint. When compared to uninfected PMN, PMN<jats:sub>HITTIN<\/jats:sub> displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log<jats:sub>2<\/jats:sub>FC of 0.2, FDR &lt; 0.05) whereas PMN<jats:sub>HIT<\/jats:sub> demonstrated 3816 significantly upregulated and 3794 significantly downregulated DEGs following 6h <jats:italic>Mtb<\/jats:italic> infection. Contrasting the log<jats:sub>2<\/jats:sub>FC 6h infection response to <jats:italic>Mtb<\/jats:italic> from PMN<jats:sub>HITTIN<\/jats:sub> against PMN<jats:sub>HIT<\/jats:sub>, 2285 genes showed significant differential response between the two groups. Overall PMN<jats:sub>HITTIN<\/jats:sub> had a lower fold change response to <jats:italic>Mtb<\/jats:italic> infection compared to PMN<jats:sub>HIT<\/jats:sub>. According to pathway enrichment, Apoptosis and NETosis were differentially regulated between HITTIN and HIT PMN responses after 6h <jats:italic>Mtb<\/jats:italic> infection. To corroborate the blunted NETosis transcriptional response measured among HITTIN, fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMN<jats:sub>HITTIN<\/jats:sub> compared to PMN<jats:sub>HIT<\/jats:sub>, showing that PMN<jats:sub>HITTIN<\/jats:sub> have a distinct response to <jats:italic>Mtb<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010888","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T17:52:22Z","timestamp":1692899542000},"page":"e1010888","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neutrophil extracellular trap formation and gene programs distinguish TST\/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8551-3301","authenticated-orcid":true,"given":"Elouise E.","family":"Kroon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilian","family":"Correa-Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7956-5481","authenticated-orcid":true,"given":"Rachel","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5332-3722","authenticated-orcid":true,"given":"Allison","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-7011","authenticated-orcid":true,"given":"Lize","family":"Engelbrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen A.","family":"Kriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-373X","authenticated-orcid":true,"given":"Ben","family":"Loos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-6152","authenticated-orcid":true,"given":"Naomi","family":"Okugbeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-938X","authenticated-orcid":true,"given":"Marianna","family":"Orlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Cassart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Kinnear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-0806","authenticated-orcid":true,"given":"Gerard C.","family":"Tromp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-6741","authenticated-orcid":true,"given":"Marlo","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-2621","authenticated-orcid":true,"given":"Anna K.","family":"Coussens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2640-536X","authenticated-orcid":true,"given":"Erwin","family":"Schurr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6444-5688","authenticated-orcid":true,"given":"Eileen G.","family":"Hoal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"pgen.1010888.ref001","unstructured":"WHO W. 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