{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:46:59Z","timestamp":1777924019833,"version":"3.51.4"},"reference-count":79,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:p>\n                    Tuberculosis (TB) caused by\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) kills 1.6 million people worldwide every year, and there is an urgent need for targeting host\u2013pathogen interactions as a strategy to reduce mycobacterial resistance to current antimicrobials. Noncoding RNAs are emerging as important regulators of numerous biological processes and avenues for exploitation in host-directed therapeutics. Although long noncoding RNAs (lncRNAs) are abundantly expressed in immune cells, their functional role in gene regulation and bacterial infections remains understudied. In this study, we identify an immunoregulatory long intergenic noncoding RNA, lincRNA-MIR99AHG, which is upregulated in mouse and human macrophages upon IL-4\/IL-13 stimulation and downregulated after clinical Mtb HN878 strain infection and in peripheral blood mononuclear cells from active TB patients. To evaluate the functional role of lincRNA-MIR99AHG, we used antisense locked nucleic acid (LNA) GapmeR-mediated antisense oligonucleotide (ASO) lncRNA knockdown experiments. Knockdown of lincRNA-MIR99AHG with ASOs significantly reduced intracellular Mtb growth in mouse and human macrophages and reduced pro-inflammatory cytokine production. In addition,\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    treatment of mice with MIR99AHG ASOs reduced the mycobacterial burden in the lung and spleen. Furthermore, in macrophages, lincRNA-MIR99AHG is translocated to the nucleus and interacts with high affinity to hnRNPA2\/B1 following IL-4\/IL-13 stimulation and Mtb HN878 infection. Together, these findings identify lincRNA-MIR99AHG as a positive regulator of inflammation and macrophage polarization to promote Mtb growth and a possible target for adjunctive host-directed therapy against TB.\n                  <\/jats:p>","DOI":"10.1089\/nat.2022.0009","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T12:53:11Z","timestamp":1658926391000},"page":"421-437","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Host-Directed Targeting of LincRNA-MIR99AHG Suppresses Intracellular Growth of\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1177","volume":"32","author":[{"given":"Lorna","family":"Gcanga","sequence":"first","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Department of Pathology, Cape Town Component, Cape Town, South Africa."},{"name":"Division of Immunology, Department of 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Douala, Douala, Cameroon."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mumin","family":"Ozturk","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Department of Pathology, Cape Town Component, Cape Town, South Africa."},{"name":"Division of Immunology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa."},{"name":"Immunology of Infectious Diseases, Faculty of Health Sciences, South African Medical Research Council (SAMRC) University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shandre","family":"Pillay","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Department of Pathology, Cape Town Component, Cape Town, South Africa."},{"name":"Division of Immunology, Department of Pathology, 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Ebua","family":"Chia","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Department of Pathology, Cape Town Component, Cape Town, South Africa."},{"name":"Division of Immunology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa."},{"name":"Immunology of Infectious Diseases, Faculty of Health Sciences, South African Medical Research Council (SAMRC) University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley Kimbung","family":"Mbandi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pathology, South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South 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Tropical medicine, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Schmeier","sequence":"additional","affiliation":[{"name":"College of Science, School of Natural and Computational Sciences, Massey University, Auckland, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanvir","family":"Alam","sequence":"additional","affiliation":[{"name":"Information and Computing Technology Division, College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sugata","family":"Roy","sequence":"additional","affiliation":[{"name":"RIKEN Center for Integrative Medical Sciences, Cellular Function Conversion Technology Team, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harukazu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"RIKEN Center for Integrative Medical Sciences, Cellular Function Conversion Technology Team, Yokohama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), Department of Pathology, Cape Town Component, Cape Town, South Africa."},{"name":"Division of Immunology, Department of Pathology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa."},{"name":"Immunology of Infectious Diseases, Faculty of Health Sciences, South African Medical Research Council (SAMRC) University of Cape Town, Cape Town, South Africa."},{"name":"Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine (IDM), Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South 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