{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:29:40Z","timestamp":1789111780789,"version":"build-2803163510"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI155621"],"award-info":[{"award-number":["R01AI155621"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["F31AI176795"],"award-info":[{"award-number":["F31AI176795"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["F31AI176821"],"award-info":[{"award-number":["F31AI176821"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["F31AI179168"],"award-info":[{"award-number":["F31AI179168"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013301","name":"Parkinson's Foundation","doi-asserted-by":"crossref","award":["938138"],"award-info":[{"award-number":["938138"]}],"id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | Office of the Assistant Secretary for Health","award":["W81XWH-20-1-0150"],"award-info":[{"award-number":["W81XWH-20-1-0150"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,3,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The genetic and molecular determinants that underlie the heterogeneity of\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              (Mtb) infection outcomes in humans are poorly understood. Multiple lines of evidence demonstrate that mitochondrial dysfunction can exacerbate mycobacterial disease severity, and mutations in some mitochondrial genes confer susceptibility to mycobacterial infection in humans. Here, we report that mutations in mitochondria DNA (mtDNA) polymerase gamma potentiate susceptibility to Mtb infection in mice. Polg\n              <jats:sup>D257A<\/jats:sup>\n              mutator mtDNA mice fail to mount a protective innate immune response at an early infection time point, evidenced by high bacterial burdens, reduced M1 macrophages, and excessive neutrophil infiltration in the lungs. Immunohistochemistry reveals signs of enhanced necrosis in the lungs of Mtb-infected Polg\n              <jats:sup>D257A<\/jats:sup>\n              mice, and Polg\n              <jats:sup>D257A<\/jats:sup>\n              mutator macrophages are hypersusceptible to extrinsic triggers of necroptosis\n              <jats:italic>ex vivo<\/jats:italic>\n              . By assigning a role for mtDNA mutations in driving necrosis during Mtb infection, this work further highlights the requirement for mitochondrial homeostasis in mounting balanced immune responses to Mtb.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00324-24","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T14:00:11Z","timestamp":1739973611000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Necrosis drives susceptibility to\n            <i>Mycobacterium tuberculosis<\/i>\n            in Polg\n            <sup>D257A<\/sup>\n            mutator mice"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-8398","authenticated-orcid":false,"given":"C. J.","family":"Mabry","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. G.","family":"Weindel","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. W.","family":"Stranahan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, Texas A&M College of Veterinary Medicine and Biomedical Sciences","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"VanPortfliet","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]},{"name":"The Jackson Laboratory","place":["Bar Harbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. R.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. L.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]},{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. P.","family":"West","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]},{"name":"The Jackson Laboratory","place":["Bar Harbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2442-4679","authenticated-orcid":false,"given":"K. L.","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4976-0759","authenticated-orcid":true,"given":"R. O.","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health, College of Medicine","place":["Bryan, USA"]},{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01839-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-017-0424-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe7548"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14156"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04180-w"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.128.4.355"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.10.006"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2014.02.009"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47190-y"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109989"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.09.001"},{"key":"e_1_3_4_13_2","unstructured":"World Health Organization. 2023. Global tuberculosis report 2023. Geneva Switzerland World Health Organization"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1260859"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00687-20"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.06.009"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.022"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01523-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.020867"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.3.4.415"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16143-6"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba4733"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.004"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2017.1377881"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181776"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102366"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.038"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112125"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-169474"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13669"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.05.11.593693"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2203855119"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06074-z"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1805"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03387-9"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129744"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.635335"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11030631"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab729"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.712457"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.09.003"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02517"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.3"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227454"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.11.014"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.008"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201603040"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.09.011"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51071"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39169"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109195"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.01.010"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.05.004"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02326"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901805116"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.11.012"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.09.014"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0101-0"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00324-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00324-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T11:27:51Z","timestamp":1743679671000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00324-24"}},"subtitle":[],"editor":[{"given":"Padmini","family":"Salgame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,11]]}},"alternative-id":["10.1128\/iai.00324-24"],"URL":"https:\/\/doi.org\/10.1128\/iai.00324-24","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"2024-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00324-24"}}