{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T21:48:18Z","timestamp":1778190498072,"version":"3.51.4"},"reference-count":98,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Delayed-type hypersensitivity (DTH) to Mycobacterium tuberculosis (MTb) antigens is a crucial component of the cellular immune response presented during tuberculosis infection. This reaction is driven primarily by T lymphocytes, which recognize mycobacterial antigens and trigger a focused inflammatory cascade. Cytokines produced by T lymphocytes stimulate the formation of granulomas, organized structures that help contain the bacteria and prevent their spread. DTH is essential for controlling the infection and forms the basis of diagnostic tools, including the still widely practiced tuberculin skin test despite its limitations. This immunological mechanism is also used as an important therapeutic target in the treatment of tuberculosis by modulating the cellular response. These approaches include immunomodulatory agents, therapeutic vaccines and host-directed treatment. Ongoing research offers promising opportunities for future interventions aimed at decreasing the global mortality associated with tuberculosis.<\/jats:p>","DOI":"10.3390\/ijms27062620","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:26:19Z","timestamp":1773390379000},"page":"2620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Delayed-Type Hypersensitivity to Mycobacterium tuberculosis Antigens: The Immunological Mechanism and Potential Therapeutic Strategies\u2014A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1827-6387","authenticated-orcid":false,"given":"Wiktoria","family":"Andryszkiewicz","sequence":"first","affiliation":[{"name":"Student Research Group of Allergology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5344-0398","authenticated-orcid":false,"given":"Maksym","family":"Bodziony","sequence":"additional","affiliation":[{"name":"Student Research Group of Allergology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Chmielewska","sequence":"additional","affiliation":[{"name":"Student Research Group of Allergology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5505-2776","authenticated-orcid":false,"given":"Martyna","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Student Research Group of Allergology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Rzo\u0144ca","sequence":"additional","affiliation":[{"name":"Student Research Group of Allergology and Internal Medicine, Faculty of Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7218-2961","authenticated-orcid":false,"given":"Krzysztof","family":"Gomu\u0142ka","sequence":"additional","affiliation":[{"name":"Clinical Department of Allergology and Internal Medicine, Institute of Internal Medicine, Wroclaw Medical University, 50-556 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106324","DOI":"10.1016\/j.micpath.2023.106324","article-title":"Harnessing Actinobacteria Potential for Cancer Prevention and Treatment","volume":"183","author":"Pongen","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/1469-0691.12555","article-title":"Steps towards the Discovery of Mycobacterium tuberculosis by Robert Koch, 1882","volume":"20","author":"Cambau","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Deol, A.K., Shaikh, N., Middelkoop, K., Mohlamonyane, M., White, R.G., and McCreesh, N. (2022). Importance of Ventilation and Occupancy to Mycobacterium tuberculosis Transmission Rates in Congregate Settings. BMC Public Health, 22.","DOI":"10.1186\/s12889-022-14133-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.59556\/japi.73.1113","article-title":"Transmission of Mycobacterium tuberculosis","volume":"73","author":"Sarkar","year":"2025","journal-title":"J. Assoc. Physicians India"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Coleman, M., Martinez, L., Theron, G., Wood, R., and Marais, B. (2022). Mycobacterium tuberculosis Transmission in High-Incidence Settings\u2014New Paradigms and Insights. Pathogens, 11.","DOI":"10.3390\/pathogens11111228"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/femsre\/fux011","article-title":"Antimicrobial Resistance in Mycobacterium tuberculosis: Mechanistic and Evolutionary Perspectives","volume":"41","author":"Gygli","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nasiri, M.J., Haeili, M., Ghazi, M., Goudarzi, H., Pormohammad, A., Imani Fooladi, A.A., and Feizabadi, M.M. (2017). New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00681"},{"key":"ref_8","first-page":"CD016013","article-title":"Diabetes as a Risk Factor for Tuberculosis Disease","volume":"2025","author":"Franco","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_9","first-page":"CD015890","article-title":"Undernutrition as a Risk Factor for Tuberculosis Disease","volume":"2025","author":"Franco","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yirsaw, A.N., Mengistie, B.A., Getachew, E., Mekonnen, G.B., Shibabaw, A.A., Chereka, A.A., Kitil, G.W., Wondie, W.T., and Lakew, G. (2025). Prevalence of Pulmonary Tuberculosis and Associated Factors among Adults Living with HIV\/AIDS in Ethiopia, Systematic Review and Meta-Analysis. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-024-10419-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/ije\/dyad052","article-title":"Mapping Tuberculosis Prevalence in Ethiopia Using Geospatial Meta-Analysis","volume":"52","author":"Alene","year":"2023","journal-title":"Int. J. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/cmi.12480","article-title":"The Innate Immune Response in Human Tuberculosis","volume":"17","author":"Lerner","year":"2015","journal-title":"Cell. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"470","DOI":"10.2500\/aap.2019.40.4274","article-title":"Classification of Hypersensitivity Reactions","volume":"40","author":"Dispenza","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.2500\/aap.2012.33.3561","article-title":"Chapter 28: Classification of Hypersensitivity Reactions","volume":"33","author":"Uzzaman","year":"2012","journal-title":"Allergy Asthma Proc."},{"key":"ref_15","first-page":"4","article-title":"Delayed-Type Hypersensitivity","volume":"55","author":"Luo","year":"2003","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_16","unstructured":"Marwa, K., Goldin, J., and Kondamudi, N.P. (2025). Type IV Hypersensitivity Reaction. StatPearls, StatPearls Publishing."},{"key":"ref_17","unstructured":"World Health Organization (2016). The Use of Loop-Mediated Isothermal Amplification (TB-LAMP) for the Diagnosis of Pulmonary Tuberculosis: Policy Guidance, World Health Organization."},{"key":"ref_18","first-page":"CD015806","article-title":"Low-Complexity Manual Nucleic Acid Amplification Tests for Pulmonary Tuberculosis in Children","volume":"2025","author":"Inbaraj","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_19","unstructured":"World Health Organization (2025). WHO Consolidated Guidelines on Tuberculosis: Module 3: Diagnosis, World Health Organization."},{"key":"ref_20","unstructured":"World Health Organization (2026, March 08). 2, Recommendations, WHO Consolidated Guidelines on Tuberculosis: Module 6: Tuberculosis and Comorbidities, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK619209\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/microbiolspec.GPP3-0022-2018","article-title":"Immunology of Mycobacterium tuberculosis Infections","volume":"7","author":"Sia","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10315","DOI":"10.1038\/s41598-019-46731-6","article-title":"Mechanism of Catalysis and Inhibition of Mycobacterium tuberculosis SapM, Implications for the Development of Novel Antivirulence Drugs","volume":"9","author":"Bruce","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.4049\/jimmunol.0904005","article-title":"V Mycobacterium tuberculosis and TLR2 Agonists Inhibit Induction of Type I IFN and Class I MHC Antigen Cross Processing by TLR9","volume":"185","author":"Simmons","year":"2010","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1128\/IAI.01663-07","article-title":"The Phenolic Glycolipid of Mycobacterium tuberculosis Differentially Modulates the Early Host Cytokine Response but Does Not in Itself Confer Hypervirulence","volume":"76","author":"Sinsimer","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.chom.2017.04.004","article-title":"A Rab20-Dependent Membrane Trafficking Pathway Controls M. Tuberculosis Replication by Regulating Phagosome Spaciousness and Integrity","volume":"21","author":"Schnettger","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1172\/JCI200421027","article-title":"Fatal Mycobacterium tuberculosis Infection despite Adaptive Immune Response in the Absence of MyD88","volume":"114","author":"Fremond","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6028","DOI":"10.1128\/JB.00469-07","article-title":"ESAT-6 from Mycobacterium tuberculosis Dissociates from Its Putative Chaperone CFP-10 under Acidic Conditions and Exhibits Membrane-Lysing Activity","volume":"189","author":"Fretz","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1128\/AAC.43.2.403","article-title":"Mycobacteriocidal Action of Exogenous Nitric Oxide","volume":"43","author":"Long","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1378\/chest.09-0903","article-title":"Neutrophils Are the Predominant Infected Phagocytic Cells in the Airways of Patients With Active Pulmonary TB","volume":"137","author":"Eum","year":"2009","journal-title":"Chest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14459","DOI":"10.1073\/pnas.96.25.14459","article-title":"Toll-like Receptor-2 Mediates Mycobacteria-Induced Proinflammatory Signaling in Macrophages","volume":"96","author":"Underhill","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1128\/IAI.00057-06","article-title":"Genetically Determined Susceptibility to Tuberculosis in Mice Causally Involves Accelerated and Enhanced Recruitment of Granulocytes","volume":"74","author":"Keller","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1002\/eji.201040433","article-title":"Enhanced Protection to Mycobacterium tuberculosis Infection in IL-10-deficient Mice Is Accompanied by Early and Enhanced Th1 Responses in the Lung","volume":"40","author":"Redford","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.tube.2009.01.001","article-title":"Lack of IL-10 Alters Inflammatory and Immune Responses during Pulmonary Mycobacterium tuberculosis Infection","volume":"89","author":"Higgins","year":"2009","journal-title":"Tuberculosis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.4049\/jimmunol.181.8.5545","article-title":"Interleukin-10 Promotes Mycobacterium Tuberculosis Disease Progression in CBA\/J Mice","volume":"181","author":"Beamer","year":"2008","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.immuni.2019.03.024","article-title":"Transforming Growth Factor-\u03b2 Signaling in Immunity and Cancer","volume":"50","author":"Batlle","year":"2019","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.imlet.2004.09.008","article-title":"TNF-\u03b1, TGF-\u03b2 and NO Relationship in Sera from Tuberculosis (TB) Patients of Different Severity","volume":"98","author":"Fiorenza","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.1365-2249.2006.03049.x","article-title":"A Combination of a Transforming Growth Factor-\u03b2 Antagonist and an Inhibitor of Cyclooxygenase Is an Effective Treatment for Murine Pulmonary Tuberculosis","volume":"144","author":"Maldonado","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1093\/ofid\/ofy209.036","article-title":"166. TGF-\u03b2 Restricts T-Cell IFNg Production in Pulmonary Tuberculous Granulomas","volume":"5","author":"Gern","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1084\/jem.178.6.2249","article-title":"An Essential Role for Interferon Gamma in Resistance to Mycobacterium tuberculosis Infection","volume":"178","author":"Flynn","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"745483","DOI":"10.1155\/2012\/745483","article-title":"Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis","volume":"2012","author":"Cavalcanti","year":"2012","journal-title":"Pulm. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.chom.2021.02.005","article-title":"TGF\u03b2 Restricts Expansion, Survival, and Function of T Cells within the Tuberculous Granuloma","volume":"29","author":"Gern","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/mi.2011.7","article-title":"The Role of IL-10 in Immune Regulation during M. tuberculosis Infection","volume":"4","author":"Redford","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Singh, A., Dey, A.B., Mohan, A., Sharma, P.K., and Mitra, D.K. (2012). Foxp3+ Regulatory T Cells among Tuberculosis Patients: Impact on Prognosis and Restoration of Antigen Specific IFN-\u03b3 Producing T Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044728"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1084\/jem.20091885","article-title":"Pathogen-Specific Regulatory T Cells Delay the Arrival of Effector T Cells in the Lung during Early Tuberculosis","volume":"207","author":"Shafiani","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/ni.1904","article-title":"Eicosanoid Pathways Regulate Adaptive Immunity to Mycobacterium tuberculosis","volume":"11","author":"Divangahi","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1002\/eji.201343751","article-title":"The Who\u2019s Who of T-cell Differentiation: Human Memory T-cell Subsets","volume":"43","author":"Mahnke","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1128\/iai.62.5.1683-1690.1994","article-title":"Evolution of CD4 T-Cell Subsets Following Infection of Naive and Memory Immune Mice with Mycobacterium tuberculosis","volume":"62","author":"Griffin","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1128\/IAI.68.2.621-629.2000","article-title":"CD4+ T-Cell Subsets That Mediate Immunological Memory to Mycobacterium tuberculosis Infection in Mice","volume":"68","author":"Andersen","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Brighenti, S., and Ordway, D.J. (2016). Regulation of Immunity to Tuberculosis. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.TBTB2-0006-2016"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1365-3083.2010.02496.x","article-title":"T Regulatory Cells and Immune Activation in Mycobacterium tuberculosis Infection and the Effect of Preventive Therapy","volume":"73","author":"Wergeland","year":"2011","journal-title":"Scand. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tube.2012.02.008","article-title":"A Mouse Model of Tuberculosis Reinfection","volume":"92","author":"Ordway","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.imlet.2006.08.002","article-title":"Mantoux Test as a Model for a Secondary Immune Response in Humans","volume":"107","author":"Reed","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/2229-5178.93479","article-title":"Mantoux Test and Its Interpretation","volume":"3","author":"Nayak","year":"2012","journal-title":"Indian Dermatol. Online J."},{"key":"ref_54","first-page":"85","article-title":"Role of Mantoux Test in the Diagnosis of Tuberculosis","volume":"6","author":"Loh","year":"2011","journal-title":"Malays. Fam. Physician"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1164\/ajrccm.162.4.9912048","article-title":"Does Size Matter? Utility of Size of Tuberculin Reactions for the Diagnosis of Mycobacterial Disease","volume":"162","author":"Menzies","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","unstructured":"Cohn, D.L., O\u2019Brien, R.J., Geiter, L.J., Gordin, F.M., Hershfield, E., Horsburgh, C.R., Jereb, J.A., Jordan, T.J., Kaplan, J.E., and Nolan, C.M. (2025, December 08). Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection, Available online: https:\/\/www.cdc.gov\/mmwr\/preview\/mmwrhtml\/rr4906a1.htm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1164\/ajrccm.161.4.16141","article-title":"Diagnostic Standards and Classification of Tuberculosis in Adults and Children","volume":"161","author":"Dunlap","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4103\/1817-1737.44778","article-title":"Diagnosis of Latent Tuberculosis: Can We Do Better?","volume":"4","year":"2009","journal-title":"Ann. Thorac. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1086\/426434","article-title":"Influence of Bacille Calmette-Gu\u00e9rin Vaccination on Size of Tuberculin Skin Test Reaction: To What Size?","volume":"40","author":"Tissot","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"185","DOI":"10.7326\/0003-4819-119-3-199308010-00002","article-title":"Tuberculin and Anergy Testing in HIV-Seropositive and HIV-Seronegative Persons","volume":"119","author":"Markowitz","year":"1993","journal-title":"Ann. Intern. Med."},{"key":"ref_61","unstructured":"Pahal, P., Pollard, E.J., and Sharma, S. (2025). PPD Skin Test. StatPearls, StatPearls Publishing."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1128\/JCM.37.10.3229-3232.1999","article-title":"Evaluation of the Tuberculin Gamma Interferon Assay: Potential to Replace the Mantoux Skin Test","volume":"37","author":"Pottumarthy","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_63","first-page":"49","article-title":"Guidelines for Using the QuantiFERON\u00ae-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States","volume":"54","author":"Mazurek","year":"2005","journal-title":"MMWR Recomm. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1002\/cpt.2261","article-title":"The Treatment of Tuberculosis","volume":"110","author":"Peloquin","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.arbres.2017.02.006","article-title":"Diagn\u00f3stico y Tratamiento de La Tuberculosis Con Resistencia a F\u00e1rmacos","volume":"53","author":"Caminero","year":"2017","journal-title":"Arch. Bronconeumol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.ijtb.2021.08.034","article-title":"Changing Paradigms in the Treatment of Tuberculosis","volume":"69","author":"Chawla","year":"2022","journal-title":"Indian J. Tuberc."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jeong, E.-K., Lee, H.-J., and Jung, Y.-J. (2022). Host-Directed Therapies for Tuberculosis. Pathogens, 11.","DOI":"10.3390\/pathogens11111291"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s11154-021-09679-5","article-title":"Vitamin D, Infections and Immunity","volume":"23","author":"Ismailova","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"ofw151","DOI":"10.1093\/ofid\/ofw151","article-title":"Vitamin D as Adjunctive Host-Directed Therapy in Tuberculosis: A Systematic Review","volume":"3","author":"Wallis","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Salahuddin, N., Ali, F., Hasan, Z., Rao, N., Aqeel, M., and Mahmood, F. (2013). Vitamin D Accelerates Clinical Recovery from Tuberculosis: Results of the SUCCINCT Study [Supplementary Cholecalciferol in Recovery from Tuberculosis]. A Randomized, Placebo-Controlled, Clinical Trial of Vitamin D Supplementation in Patients with Pulmonary Tuberculosis\u2019. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-22"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.intimp.2018.09.013","article-title":"Antimicrobial and Immunomodulatory Activity Induced by Loperamide in Mycobacterial Infections","volume":"65","author":"Ruiz","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"114588","DOI":"10.1016\/j.biopha.2023.114588","article-title":"Advances in Immunomodulatory Strategies for Host-Directed Therapies in Combating Tuberculosis","volume":"162","author":"Ayodele","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"165574","DOI":"10.1016\/j.bbadis.2019.165574","article-title":"Eicosanoid Pathway on Host Resistance and Inflammation during Mycobacterium tuberculosis Infection Is Comprised by LTB4 Reduction but Not PGE2 Increment","volume":"1866","author":"Sorgi","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"dmm049018","DOI":"10.1242\/dmm.049018","article-title":"Rapamycin Modulates Pulmonary Pathology in a Murine Model of Mycobacterium tuberculosis Infection","volume":"14","author":"Bhatt","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"118314","DOI":"10.1016\/j.biopha.2025.118314","article-title":"Metformin Induces Iron Deprivation and Enhances Mitochondrial ROS in Macrophages Creating a Hostile Environment for Survival of Intracellular Mycobacterium tuberculosis","volume":"189","author":"Modanwal","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Naicker, N., Sigal, A., and Naidoo, K. (2020). Metformin as Host-Directed Therapy for TB Treatment: Scoping Review. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00435"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/infdis\/jit550","article-title":"Statin Therapy Reduces the Mycobacterium tuberculosis Burden in Human Macrophages and in Mice by Enhancing Autophagy and Phagosome Maturation","volume":"209","author":"Parihar","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_78","first-page":"7617023","article-title":"Potential Effect of Statins on Mycobacterium Tuberculosis Infection","volume":"2018","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1093\/infdis\/jiz517","article-title":"Adjunctive Host-Directed Therapy With Statins Improves Tuberculosis-Related Outcomes in Mice","volume":"221","author":"Dutta","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Leukes, V., Walzl, G., and du Plessis, N. (2020). Myeloid-Derived Suppressor Cells as Target of Phosphodiesterase-5 Inhibitors in Host-Directed Therapeutics for Tuberculosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00451"},{"key":"ref_81","first-page":"126","article-title":"Gene Expression and In Vitro Pharmacogenetic Studies of Dopamine and Serotonin Gene Receptors in Tuberculosis","volume":"20","author":"Sheikhpour","year":"2021","journal-title":"Tanaffos"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s44259-025-00143-x","article-title":"The Parkinson\u2019s Drug Benztropine Possesses Histamine Receptor 1-Dependent Host-Directed Antimicrobial Activity against Mycobacterium tuberculosis","volume":"3","author":"Sahile","year":"2025","journal-title":"npj Antimicrob. Resist."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1073\/pnas.1424563112","article-title":"Anti-Vascular Endothelial Growth Factor Treatment Normalizes Tuberculosis Granuloma Vasculature and Improves Small Molecule Delivery","volume":"112","author":"Datta","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e240236","DOI":"10.1590\/0074-02760240236","article-title":"Challenges in Developing New Tuberculosis Vaccines","volume":"120","author":"Sadigurschi","year":"2025","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/MCP.0000000000000950","article-title":"Advances in Development of New Tuberculosis Vaccines","volume":"29","author":"Onyebujoh","year":"2023","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"338","DOI":"10.25259\/IJMR_1478_2024","article-title":"TB-Vaccines: Current Status & Challenges","volume":"160","author":"Sachdeva","year":"2024","journal-title":"Indian J. Med. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Franco, A.R., and Peri, F. (2021). Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants. Cells, 10.","DOI":"10.3390\/cells10010078"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1016\/j.vaccine.2015.05.088","article-title":"Safety and Immunogenicity of Candidate Vaccine M72\/AS01E in Adolescents in a TB Endemic Setting","volume":"33","author":"Geldenhuys","year":"2015","journal-title":"Vaccine"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"126816","DOI":"10.1016\/j.vaccine.2025.126816","article-title":"Optimising the M72\/AS01E Tuberculosis Vaccine Candidate Phase 3 Trial Based on the Phase 2b Trial Results","volume":"49","author":"Dale","year":"2025","journal-title":"Vaccine"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e00439-16","DOI":"10.1128\/CVI.00439-16","article-title":"Safety and Immunogenicity of the Recombinant Mycobacterium Bovis BCG Vaccine VPM1002 in HIV-Unexposed Newborn Infants in South Africa","volume":"24","author":"Loxton","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Figl, J., K\u00f6hler, H., Wedlich, N., Liebler-Tenorio, E.M., Grode, L., Parzmair, G., Krishnamoorthy, G., Nieuwenhuizen, N.E., Kaufmann, S.H.E., and Menge, C. (2023). Safety and Immunogenicity of Recombinant Bacille Calmette-Gu\u00e9rin Strain VPM1002 and Its Derivatives in a Goat Model. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065509"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhao, H., Zhang, Z., Xue, Y., Wang, N., Liu, Y., Ma, X., Wang, L., Wang, X., Zhang, D., and Zhang, J. (2025). Evaluation of Immunogenicity of Mycobacterium tuberculosis Ag85ab DNA Vaccine Delivered by Pulmonary Administration. Vaccines, 13.","DOI":"10.3390\/vaccines13050442"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kazakova, A., Zhelnov, P., Sidorov, R., Rogova, A., Vasileva, O., Ivanov, R., Reshetnikov, V., and Muslimov, A. (2024). DNA and RNA Vaccines against Tuberculosis: A Scoping Review of Human and Animal Studies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457327"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Cardona, P., and Cardona, P.-J. (2019). Regulatory T Cells in Mycobacterium tuberculosis Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02139"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41598-018-36403-2","article-title":"PD-1\/PD-L1 Pathway Modulates Macrophage Susceptibility to Mycobacterium tuberculosis Specific CD8+ T Cell Induced Death","volume":"9","author":"Suarez","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Khan, N., Vidyarthi, A., Nadeem, S., Negi, S., Nair, G., and Agrewala, J.N. (2016). Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00529"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s00018-019-03370-4","article-title":"The Gut Microbiome in Tuberculosis Susceptibility and Treatment Response: Guilty or Not Guilty?","volume":"77","author":"Eribo","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.canlet.2019.01.032","article-title":"Drug Delivery Systems Targeting Tumor-Associated Fibroblasts for Cancer Immunotherapy","volume":"448","author":"Liu","year":"2019","journal-title":"Cancer Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:27:55Z","timestamp":1773390475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/6\/2620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":98,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27062620"],"URL":"https:\/\/doi.org\/10.3390\/ijms27062620","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]}}}