{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:55:17Z","timestamp":1791914117123,"version":"4.3.4"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004419","name":"CRDF Global","doi-asserted-by":"publisher","award":["US-INDO VAP Award 65336"],"award-info":[{"award-number":["US-INDO VAP Award 65336"]}],"id":[{"id":"10.13039\/100004419","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004419","name":"CRDF Global","doi-asserted-by":"publisher","award":["DDA 3-19-65679-1"],"award-info":[{"award-number":["DDA 3-19-65679-1"]}],"id":[{"id":"10.13039\/100004419","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cain Foundation for Infectious Disease Research"},{"name":"DBT","award":["BT\/PR9622\/MED\/15\/109\/2013"],"award-info":[{"award-number":["BT\/PR9622\/MED\/15\/109\/2013"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    We determined whether microRNAs (miRNAs) regulate resistance to\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) infection in healthy household contacts (HHCs) of patients with tuberculosis (TB). As shown in our previously published study, we recruited 460 HHCs from 443 index cases of active pulmonary TB, with 293 (64.8%) remaining IGRA-negative throughout a two-year follow-up. Whole-transcriptome sequencing at baseline (0 months) and follow-up (24 months) and confirmation studies identified miRNA-1246 (downregulated) and miRNA-125b (upregulated) as potential candidates for the development of resistance in nonconverters compared with converters and progressors. Mechanistic studies using proteomics and computational analysis revealed that miRNA-1246 inhibitor reduce Mtb growth in macrophages by regulating lipase activity, specifically through targeting alpha\/beta hydrolase domain-containing protein 2 (ABHD2). Inhibition of miRNA-1246 increased glycolytic activity and promoted a metabolic shift in macrophages conducive to pathogen clearance, suggesting its critical role in metabolic regulation and resistance to tuberculosis. These findings highlight potential miRNA-based therapeutic strategies to enhance immunity against Mtb.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014454","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:43:31Z","timestamp":1791913411000},"page":"e1014454","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA-1246 regulates macrophage lipid metabolism and is involved in resistance to human Mycobacterium tuberculosis infection"],"prefix":"10.1371","volume":"22","author":[{"given":"Ashutosh","family":"Tripathi","sequence":"first","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute","place":["Seattle, Washington, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata Sanjeev Kumar","family":"Neela","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh Kumar","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Saint Louis University School Medicine","place":["St. Louis, Missouri, United States of America"],"department":["Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamakshi Prudhula","family":"Devalraju","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anvesh Kumar","family":"Bogam","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanmoy","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research, The University of Texas Health Science Center at Tyler","place":["Tyler, Texas, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varalakshmi","family":"Mallidi","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Vankayalapati","sequence":"additional","affiliation":[{"name":"Saint Louis University School Medicine","place":["St. Louis, Missouri, United States of America"],"department":["Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Soheb Sadath","family":"Ansari","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Arana","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center","place":["Dallas, Texas, United States of America"],"department":["Department of Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhu","family":"Joshi","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karan P.","family":"Singh","sequence":"additional","affiliation":[{"name":"The University of Texas at Tyler School of Medicine, Health Science Center","place":["Tyler, Texas, United States of America"],"department":["Department of Epidemiology and Biostatistics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya Lakshmi","family":"Valluri","sequence":"additional","affiliation":[{"name":"Bhagwan Mahavir Medical Research Centre","place":["Hyderabad, India"],"department":["Immunology and Molecular Biology Department"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishna","family":"Vankayalapati","sequence":"additional","affiliation":[{"name":"Saint Louis University School Medicine","place":["St. Louis, Missouri, United States of America"],"department":["Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-2565","authenticated-orcid":true,"given":"Deepak","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Tulane University School of Medicine","place":["New Orleans, Louisiana, United States of America"],"department":["Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"ppat.1014454.ref001","volume-title":"Global Tuberculosis Report 2024","author":"World Health Organization. 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