{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:59:11Z","timestamp":1781024351110,"version":"3.54.1"},"reference-count":41,"publisher":"Microbiology Society","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,9]]},"abstract":"<jats:p>\n                    <jats:bold>Introduction.<\/jats:bold>\n                    Tuberculosis (TB) remains a major global health threat, and its control is hindered by prolonged treatment and increasing drug resistance. Helicase with zinc finger 2 (HELZ2) has recently been identified as an RNA-binding protein up-regulated after\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) infection, yet its functional contribution to host defence is not fully understood.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold>\n                    Although HELZ2 expression increases following Mtb infection, the molecular mechanism by which HELZ2 regulates macrophage immunity, particularly autophagy-mediated bacterial clearance, remains unclear.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim<\/jats:bold>\n                    . This study aimed to elucidate the role and underlying mechanism of HELZ2 in macrophage-mediated elimination of Mtb, with a specific focus on its regulation of autophagy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methodology.<\/jats:bold>\n                    HELZ2 expression was quantified in the peripheral blood of TB patients and in Mtb-infected monocyte-derived macrophages. By knocking out and overexpressing genes, phagocytosis, intracellular bacterial survival and autophagy were analysed. Co-immunoprecipitation, chromatin immunoprecipitation and dual-luciferase assays were employed to identify HELZ2-interacting proteins and downstream transcriptional targets.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results.<\/jats:bold>\n                    HELZ2 was significantly up-regulated in patient samples and infected macrophages. HELZ2 silencing impaired phagocytosis, reduced autophagic flux and increased intracellular Mtb survival. Mechanistically, HELZ2 bound to and stabilized the MYC proto-oncogene, bHLH transcription factor (MYC), which directly activated transcription of the autophagy-related gene ATG16L1. Overexpression of MYC or ATG16L1 restored the autophagy disorder caused by HELZ2 deficiency and enhanced bacterial clearance.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion.<\/jats:bold>\n                    HELZ2 enhances macrophage autophagy and promotes intracellular Mtb elimination by interacting with MYC and up-regulating ATG16L1. This newly identified HELZ2-MYC-ATG16L1 regulatory axis provides mechanistic insight into host defence and suggests a potential target for host-directed TB therapies.\n                  <\/jats:p>","DOI":"10.1099\/jmm.0.002170","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:16:44Z","timestamp":1781021804000},"source":"Crossref","is-referenced-by-count":0,"title":["Eliminate Mycobacterium tuberculosis via HELZ2 and up-regulating ATG16L1 to promote macrophage autophagy"],"prefix":"10.1099","volume":"75","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Infectious Diseases Department, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou City, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou City, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lei","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People\u2019s Hospital, Quzhou City, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73989-y"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuae006"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2024.107325"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.medmic.2024.100116"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1367092"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52130-3"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/srep19541"},{"key":"R8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1080\/17576180.2024.2349423","article-title":"Tuberculosis diagnosis versus genexpert\u00aeMTB\/RIF formats","volume":"16","author":"Khan","year":"2024","journal-title":"Bioanalysis"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-025-01150-9"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2023.10.023"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57060522"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2348505"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2021-0030"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.666293"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1233630"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1402024"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.747799"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1177\/17534259211064285"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116255"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06026-1"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01608-x"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-024-00989-x"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114831"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104278"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae523"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1186\/s13223-016-0120-6"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1582743"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.171850"},{"key":"R30","article-title":"Berbamine promotes macrophage autophagy to clear Mycobacterium tuberculosis by regulating the ROS\/ca(2+) axis","volume":"14","author":"Zhang","year":"2023","journal-title":"mBio"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108202"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1080\/20477724.2021.1878443"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.25122"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-024-00697-0"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.820095"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.636644"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01335-9"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.4c00713"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2020.101900"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.943174"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1254"}],"container-title":["Journal of Medical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.002170?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:16:45Z","timestamp":1781021805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.002170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,9]]}},"URL":"https:\/\/doi.org\/10.1099\/jmm.0.002170","relation":{},"ISSN":["0022-2615","1473-5644"],"issn-type":[{"value":"0022-2615","type":"print"},{"value":"1473-5644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}