{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:00:50Z","timestamp":1784174450291,"version":"3.55.0"},"reference-count":116,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Molecular Microbiology , Washington University in St. Louis","award":["Internal Funding"],"award-info":[{"award-number":["Internal Funding"]}]},{"DOI":"10.13039\/100007234","name":"University of Chicago","doi-asserted-by":"crossref","award":["Internal Funding"],"award-info":[{"award-number":["Internal Funding"]}],"id":[{"id":"10.13039\/100007234","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007234","name":"University of Chicago","doi-asserted-by":"crossref","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/100007234","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:p>\n                    Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>haemophilum<\/jats:italic>\n                    (\n                    <jats:italic>Mh<\/jats:italic>\n                    ,\n                    <jats:italic>n<\/jats:italic>\n                    = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in\n                    <jats:italic>GATA2<\/jats:italic>\n                    gene, which was absent in healthy controls (HCs,\n                    <jats:italic>n<\/jats:italic>\n                    = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to\n                    <jats:italic>Mh<\/jats:italic>\n                    stimulation for IL-1\u03b2, IL-6, IL-8, MIP-1\u03b1 and MIP-1\u03b2, but not to phytohemagglutinin (PHA) or another NTM,\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>abscessus<\/jats:italic>\n                    . Impaired whole blood transcriptional responses in individuals with\n                    <jats:italic>GATA2<\/jats:italic>\n                    mutation included heightened Ras-homolog (Rho) guanosine triphosphate hydrolases (GTPase) and lowered TGF-\u03b2 responses, among others. Our results highlight that, comparatively,\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>abscessus<\/jats:italic>\n                    and\n                    <jats:italic>Mh<\/jats:italic>\n                    elicit differential immune responses in humans. We identify a 23-gene signature that distinguished host response to\n                    <jats:italic>Mh<\/jats:italic>\n                    and\n                    <jats:italic>M<\/jats:italic>\n                    .\n                    <jats:italic>abscessus<\/jats:italic>\n                    and show that in vitro GATA2 siRNA knockdown indeed attenuated cytokine responses to\n                    <jats:italic>Mh<\/jats:italic>\n                    . Thus, we provide evidence that links\n                    <jats:italic>GATA2<\/jats:italic>\n                    mutation and immune dysfunction in individuals with compromised immunity to\n                    <jats:italic>Mh<\/jats:italic>\n                    infection in humans and outline host factors associated with the immune response of this clinically relevant NTM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.185582","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T16:00:21Z","timestamp":1754409621000},"source":"Crossref","is-referenced-by-count":2,"title":["GATA2 mutation is associated with immune dysfunction and increased Mycobacterium haemophilum susceptibility in immunocompromised individuals"],"prefix":"10.1172","volume":"10","author":[{"given":"Ananya","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shail B.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhimanyu","family":"Abhimanyu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6820-446X","authenticated-orcid":true,"given":"Bruce A.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine,"},{"name":"McDonnell Genome Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine,"},{"name":"McDonnell Genome Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mushtaq","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamala","family":"Thirunavukkarasu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farheen","family":"Fatma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaya K.","family":"Amarasinghe","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makedonka","family":"Mitreva","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine,"},{"name":"McDonnell Genome Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Clifford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-4982","authenticated-orcid":true,"given":"Shabaana A.","family":"Khader","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA."},{"name":"Department of Microbiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2020.05.012"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201412-559OC"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201002-0310OC"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201205-0913OC"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.14.0120"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.00681"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.144552"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3934\/microbiol.2018.3.428"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1029\/2020GH000350"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00020-11"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7196\/AJTCCM.2022.v28i2.157"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1086\/321894"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.03.004"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00813-7"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1139\/m79-033"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.3.832-834.1999"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.11.2.190-192.1980"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-00937-2"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jctube.2020.100197"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2019.03.010"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000001929"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26828"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184931"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.566190"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2021.102108"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4MA0820-655RR"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1843.2003.00471.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-051649"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw066"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0230OC"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.190041"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158630"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2011.44.6.381"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13889"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.05.024"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02014-3"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz461"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356352"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711824105"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-374363"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13317"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-016-2713-x"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.96914"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260522"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20769-4"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131207398"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1189"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1287-1292.2002"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nm1433"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003946"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.13881"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.060509"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.626431"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00721"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1085742"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01257-z"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0417-y"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006551"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.01.028"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.2021037643"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.11.013"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67290"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/srep23132"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00914.x"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106297"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit368"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.7.3336-3338.2004"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3201\/eid1101.040589"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.07.005"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00089-4"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0799-6"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-208629"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.181909"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2015.06.008"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.htct.2022.01.014"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.9.4758"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0413OC"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1021\/bi00245a015"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00002"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413461200"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102836"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2246-1"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023739"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101840200"},{"issue":"4-6","key":"B87","first-page":"217","article-title":"Activation of the AP-1 transcription factor by inflammatory cytokines of the TNF family","volume":"7","author":"Kyriakis","year":"1999","journal-title":"Gene Expr"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00542.2007"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit037"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2013.05.002"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.849583"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.9.4620"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-011-8205-2"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00423"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01757-9"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2651"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae060"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302375"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.07.068"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/srep41686"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.010"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007100"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122772"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2022.10.274"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01258-7"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.10.004"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/ng.913"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.196"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01145"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay0233"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz663"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv602"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/185582\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:20:37Z","timestamp":1779124837000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/185582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":116,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10,8]]},"published-print":{"date-parts":[[2025,10,8]]}},"alternative-id":["10.1172\/jci.insight.185582"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.185582","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,5]]},"article-number":"e185582"}}