{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T22:21:29Z","timestamp":1781130089028,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["18\/TIDA\/6026"],"award-info":[{"award-number":["18\/TIDA\/6026"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Royal City of Dublin Hospital Trust","award":["BaggotStreetHospital\/Dublin 4\/Ireland"],"award-info":[{"award-number":["BaggotStreetHospital\/Dublin 4\/Ireland"]}]},{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["GOIPD\/2020\/16"],"award-info":[{"award-number":["GOIPD\/2020\/16"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis (TB) remains a global health challenge. Patients with drug-sensitive and drug-resistant TB undergo long, arduous, and complex treatment regimens, often involving multiple antimicrobials. While these drugs were initially implemented based on their bactericidal effects, some studies show that TB antimicrobials can also directly affect cells of the immune system, altering their immune function. As use of these antimicrobials has been the mainstay of TB therapy for over fifty years now, it is more important than ever to understand how these antimicrobials affect key pathways of the immune system. One such central pathway, which underpins the immune response to a variety of infections, is immunometabolism, namely glycolysis and oxidative phosphorylation (OXPHOS). We hypothesise that in addition to their direct bactericidal effect on Mycobacterium tuberculosis (Mtb), current TB antimicrobials can modulate immunometabolic profiles and alter mitochondrial function in primary human macrophages. Human monocyte-derived macrophages (hMDMs) were differentiated from PBMCs isolated from healthy blood donors, and treated with four first-line and six second-line TB antimicrobials three hours post stimulation with either iH37Rv-Mtb or lipopolysaccharide (LPS). 24 h post stimulation, baseline metabolism and mitochondrial function were determined using the Seahorse Extracellular Flux Analyser. The effect of these antimicrobials on cytokine and chemokine production was also assayed using Meso Scale Discovery Multi-Array technology. We show that some of the TB antimicrobials tested can significantly alter OXPHOS and glycolysis in uninfected, iH37Rv-Mtb, and LPS-stimulated hMDMs. We also demonstrate how these antimicrobial-induced immunometabolic effects are linked with alterations in mitochondrial function. Our results show that TB antimicrobials, specifically clofazimine, can modify host immunometabolism and mitochondrial function. Moreover, clofazimine significantly increased the production of IL-6 in human macrophages that were stimulated with iH37Rv-Mtb. This provides further insight into the use of some of these TB antimicrobials as potential host-directed therapies in patients with early and active disease, which could help to inform TB treatment strategies in the future.<\/jats:p>","DOI":"10.3390\/ijms222212189","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:02:41Z","timestamp":1636671761000},"page":"12189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Effect of Tuberculosis Antimicrobials on the Immunometabolic Profiles of Primary Human Macrophages Stimulated with Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-9627","authenticated-orcid":false,"given":"Christina","family":"Cahill","sequence":"first","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-3836","authenticated-orcid":false,"given":"D\u00f3nal J.","family":"Cox","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-4374","authenticated-orcid":false,"given":"Fiona","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James\u2019s Hospital, Dublin 8, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-6665","authenticated-orcid":false,"given":"Sharee A.","family":"Basdeo","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl M.","family":"Gogan","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cilian","family":"\u00d3\u2019Maoldomhnaigh","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacintha","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, St James\u2019s Hospital, Dublin 8, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Keane","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-2002","authenticated-orcid":false,"given":"James J.","family":"Phelan","sequence":"additional","affiliation":[{"name":"TB Immunology Group, Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","first-page":"2203","article-title":"Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents","volume":"12","author":"Chimbayo","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3389\/fimmu.2021.660916","article-title":"Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis","volume":"12","author":"Krug","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s12931-020-01488-9","article-title":"The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: A systematic review and meta-analysis","volume":"21","author":"Hayford","year":"2020","journal-title":"Respir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.3389\/fimmu.2020.01609","article-title":"Inhibiting Histone Deacetylases in Human Macrophages Promotes Glycolysis, IL-1\u03b2, and T Helper Cell Responses to Mycobacterium tuberculosis","volume":"11","author":"Cox","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cahill, C., O\u2019Connell, F., Gogan, K.M., Cox, D.J., Basdeo, S.A., O\u2019Sullivan, J., Gordon, S.V., Keane, J., and Phelan, J.J. (2021). The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062938"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"836","DOI":"10.3389\/fimmu.2020.00836","article-title":"Desferrioxamine Supports Metabolic Function in Primary Human Macrophages Infected With Mycobacterium tuberculosis","volume":"11","author":"Phelan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.3389\/fimmu.2018.02296","article-title":"Modulating Iron for Metabolic Support of TB Host Defense","volume":"9","author":"Phelan","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.3389\/fimmu.2020.01790","article-title":"Host-Directed Therapy in Tuberculosis: Targeting Host Metabolism","volume":"11","author":"Kim","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3389\/fcimb.2020.00493","article-title":"Understanding and Exploiting the Effect of Tuberculosis Antimicrobials on Host Mitochondrial Function and Bioenergetics","volume":"10","author":"Cahill","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.4049\/jimmunol.1501612","article-title":"Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication","volume":"196","author":"Gleeson","year":"2016","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1165\/rcmb.2018-0162OC","article-title":"Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium tuberculosis Infection","volume":"59","author":"Gleeson","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.mito.2009.11.004","article-title":"Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity","volume":"10","author":"Guillet","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3109\/01480545.2015.1092039","article-title":"Mitochondrial oxidative stress and dysfunction induced by isoniazid: Study on isolated rat liver and brain mitochondria","volume":"39","author":"Ahadpour","year":"2016","journal-title":"Drug Chem. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jhep.2006.01.027","article-title":"Mitochondrial oxidative stress and permeability transition in isoniazid and rifampicin induced liver injury in mice","volume":"45","author":"Chowdhury","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1128\/AAC.01693-16","article-title":"Liver Fatty Acid Binding Protein Deficiency Provokes Oxidative Stress, Inflammation, and Apoptosis-Mediated Hepatotoxicity Induced by Pyrazinamide in Zebrafish Larvae","volume":"60","author":"Zhang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","first-page":"1155","article-title":"Mitochondria are targets for the antituberculosis drug rifampicin in cultured epithelial cells","volume":"78","author":"Erokhina","year":"2013","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bbamem.2018.06.012","article-title":"Effect of bedaquiline on the functions of rat liver mitochondria","volume":"1861","author":"Belosludtsev","year":"2019","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.18632\/aging.100983","article-title":"Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs)","volume":"8","author":"Fiorillo","year":"2016","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/ijc.2910560624","article-title":"Clofazimine alters the energy metabolism and inhibits the growth rate of a human lung-cancer cell line in vitro and in vivo","volume":"56","author":"Plumb","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1086\/501356","article-title":"Linezolid-induced inhibition of mitochondrial protein synthesis","volume":"42","author":"Coster","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1128\/AAC.48.6.1974-1982.2004","article-title":"Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: Inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines","volume":"48","author":"Weiss","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1093\/jac\/dkx022","article-title":"Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic\/pharmacodynamic parameters","volume":"72","author":"Cavanaugh","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/cid\/ciy1068","article-title":"Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades","volume":"69","author":"Forsman","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/jac\/44.3.393","article-title":"Activity of moxifloxacin against mycobacteria","volume":"44","author":"Gillespie","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.5588\/ijtld.16.0304","article-title":"Pyrazinamide susceptibility testing in Mycobacterium tuberculosis using the fast resazurin microtiter assay plate","volume":"20","author":"Pina","year":"2016","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-695X.1998.tb01161.x","article-title":"Synergistic activities of antituberculous drugs with cerulenin and trans-cinnamic acid against Mycobacterium tuberculosis","volume":"21","author":"Rastogi","year":"1998","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.3389\/fmicb.2018.01898","article-title":"Mycobacterial Cell Wall Synthesis Inhibitors Cause Lethal ATP Burst","volume":"9","author":"Shetty","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Carmona, J., Cruz, A., Moreira-Teixeira, L., Sousa, C., Sousa, J., Osorio, N.S., Saraiva, A.L., Svenson, S., Kallenius, G., and Pedrosa, J. (2013). Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067277"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.canlet.2014.07.035","article-title":"Differential expression of mitochondrial energy metabolism profiles across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett\u2019s oesophagus","volume":"354","author":"Phelan","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"860","DOI":"10.3389\/fimmu.2018.00860","article-title":"Ferritin H Deficiency in Myeloid Compartments Dysregulates Host Energy Metabolism and Increases Susceptibility to Mycobacterium tuberculosis Infection","volume":"9","author":"Reddy","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arcmed.2005.05.022","article-title":"Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells","volume":"37","year":"2006","journal-title":"Arch. Med. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e55692","DOI":"10.7554\/eLife.55692","article-title":"The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection","volume":"9","author":"Coya","year":"2020","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.chom.2012.03.008","article-title":"Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action","volume":"11","author":"Kim","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1128\/AAC.00265-16","article-title":"Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State","volume":"60","author":"Yoon","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1179\/joc.2004.16.4.357","article-title":"Immunomodulating activity of rifampicin","volume":"16","author":"Ziglam","year":"2004","journal-title":"J. Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e39169","DOI":"10.7554\/eLife.39169","article-title":"Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages","volume":"7","author":"Cumming","year":"2018","journal-title":"Elife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1080\/14740338.2017.1335305","article-title":"Linezolid-induced lactic acidosis: The thin line between bacterial and mitochondrial ribosomes","volume":"16","author":"Santini","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.xphs.2016.12.009","article-title":"Macrophage-Mediated Clofazimine Sequestration Is Accompanied by a Shift in Host Energy Metabolism","volume":"106","author":"Trexel","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: Mutations in Tlr4 gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ijmyco.2016.06.001","article-title":"Assuming the role of mitochondria in mycobacterial infection","volume":"5","author":"Dubey","year":"2016","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E7073","DOI":"10.1073\/pnas.1521988112","article-title":"Antiinfectives targeting enzymes and the proton motive force","volume":"112","author":"Feng","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1021\/mp200101b","article-title":"Molecular imaging of intracellular drug-membrane aggregate formation","volume":"8","author":"Baik","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1128\/iai.65.11.4843-4849.1997","article-title":"Lethal tuberculosis in interleukin-6-deficient mutant mice","volume":"65","author":"Ladel","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.183.4.1345","article-title":"Impaired neutrophil response and CD4+ T helper cell 1 development in interleukin 6-deficient mice infected with Candida albicans","volume":"183","author":"Romani","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"508","DOI":"10.4049\/jimmunol.140.2.508","article-title":"B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes","volume":"140","author":"Takai","year":"1988","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1084\/jem.167.4.1417","article-title":"T cell growth and differentiation induced by interleukin-HP1\/IL-6, the murine hybridoma\/plasmacytoma growth factor","volume":"167","author":"Uyttenhove","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3892\/ijo.2015.3225","article-title":"Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer","volume":"48","author":"Han","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1272\/jnms.77.97","article-title":"Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase-3","volume":"77","author":"Ando","year":"2010","journal-title":"J. Nippon Med. Sch."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ebiom.2017.10.018","article-title":"Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial","volume":"25","author":"Sigal","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/SHK.0000000000000253","article-title":"Macrophage-derived chemokine (CCL22) is a novel mediator of lung inflammation following hemorrhage and resuscitation","volume":"42","author":"Richter","year":"2014","journal-title":"Shock"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/intimm\/11.1.81","article-title":"Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine","volume":"11","author":"Imai","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.3389\/fimmu.2021.657261","article-title":"The Warburg Effect Occurs Rapidly in Stimulated Human Adult but Not Umbilical Cord Blood Derived Macrophages","volume":"12","author":"Maoldomhnaigh","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.3389\/fimmu.2021.663695","article-title":"Lactate Alters Metabolism in Human Macrophages and Improves Their Ability to Kill Mycobacterium tuberculosis","volume":"12","author":"Maoldomhnaigh","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1016\/j.celrep.2019.11.034","article-title":"Compromised Metabolic Reprogramming Is an Early Indicator of CD8(+) T Cell Dysfunction during Chronic Mycobacterium tuberculosis Infection","volume":"29","author":"Russell","year":"2019","journal-title":"Cell Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:20Z","timestamp":1760167700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":54,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212189"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212189","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}