{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:21:43Z","timestamp":1787556103382,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Tuberculosis (TB) remains a major infectious cause of morbidity and mortality, while current diagnostic and treatment-monitoring pathways remain largely pathogen-centered. Microbiological tests are indispensable for confirming TB and detecting drug resistance, but they do not directly measure host inflammatory activity, disease-stage heterogeneity, risk of progression, biological response to therapy, or recurrence after treatment completion. Host-response biomarkers, particularly blood transcriptomic signatures, provide a complementary route toward precision TB medicine. Recent multicenter validation studies, household-contact cohorts, treatment-monitoring analyses, cell-free RNA profiling, single-cell studies, and recurrence cohorts have refined the translational evidence base for immune transcriptomic biomarkers. Across studies, active and progressive TB is characterized by interferon-inducible transcription, inflammatory myeloid remodeling, neutrophil and monocyte activation, antigen-specific T-cell activation, and partial normalization during effective therapy. These signals can support clinically relevant use cases, including sputum-independent triage of symptomatic patients, short-term prediction of progression among exposed contacts, identification of subclinical or incipient disease biology, treatment-response monitoring, and post-treatment recurrence detection. However, implementation is constrained by imperfect specificity against non-TB inflammation, heterogeneity across HIV, diabetes, pediatric, extrapulmonary and geographically diverse populations, assay standardization requirements, and limited interventional evidence. This Mini Review synthesizes recent evidence and proposes a focused translational framework linking immune transcriptomic mechanisms to actionable clinical risk stratification in TB.<\/jats:p>","DOI":"10.3389\/fcell.2026.1916291","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:53:51Z","timestamp":1787554431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Host-response biomarkers for precision tuberculosis: from immune transcriptomic signatures to clinical risk stratification"],"prefix":"10.3389","volume":"14","author":[{"given":"Nan","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Tuberculosis, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinlong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiusong","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Affiliated Hospital of Hebei University","place":["Baoding, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s44350-025-00006-5","article-title":"The relevance of biomarkers for diagnosis, monitoring treatment response and immunity during tuberculosis infections","volume":"1","author":"Barnie","year":"2025","journal-title":"Mycobacteria"},{"key":"B2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/s43856-026-01424-w","article-title":"Host response biomarkers of tuberculosis recurrence and treatment failure","volume":"6","author":"Bauer","year":"2026","journal-title":"Commun. Med. (Lond)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13646","DOI":"10.1038\/s41598-021-93059-1","article-title":"Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring","volume":"11","author":"Bayaa","year":"2021","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e20250466","DOI":"10.1084\/jem.20250466","article-title":"Type I IFN drives neutrophil swarming, impeding lung T cell-macrophage interactions and TB control","volume":"222","author":"Branchett","year":"2025","journal-title":"J. Exp. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2400457","DOI":"10.1183\/13993003.00457-2024","article-title":"Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after eight weeks of anti-tuberculous treatment","volume":"64","author":"Calderwood","year":"2024","journal-title":"Eur. Respir. J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4949","DOI":"10.1038\/s41467-024-49245-6","article-title":"Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis","volume":"15","author":"Chang","year":"2024","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1016\/j.chom.2024.11.008","article-title":"Type I IFN-Mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation","volume":"32","author":"Chowdhury","year":"2024","journal-title":"Cell Host Microbe"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.3390\/biomedicines13092076","article-title":"The evolving landscape of host biomarkers for diagnosis and monitoring of tuberculosis","volume":"13","author":"Cui","year":"2025","journal-title":"Biomedicines"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1375","DOI":"10.1002\/ctm2.1375","article-title":"Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity","volume":"13","author":"Eckold","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0078624","DOI":"10.1128\/jcm.00786-24","article-title":"Host blood protein biomarkers to screen for tuberculosis disease: a systematic review and meta-analysis","volume":"62","author":"Gaeddert","year":"2024","journal-title":"J. Clin. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"954221","DOI":"10.3389\/fimmu.2022.954221","article-title":"Whole transcriptome sequencing reveals neutrophils' transcriptional landscape associated with active tuberculosis","volume":"13","author":"Geng","year":"2022","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"101186","DOI":"10.1016\/j.lanmic.2025.101186","article-title":"Single-gene transcripts for subclinical tuberculosis: an individual participant data meta-analysis","volume":"6","author":"Greenan-Barrett","year":"2025","journal-title":"Lancet Microbe"},{"key":"B13","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/S2213-2600(19)30282-6","article-title":"Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis","volume":"8","author":"Gupta","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"115096","DOI":"10.1016\/j.isci.2026.115096","article-title":"Plasma protein biomarkers predictive of progression to active tuberculosis among close contacts of patients with tuberculosis","volume":"29","author":"Han","year":"","journal-title":"iScience."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1186\/s12879-026-13179-9","article-title":"Identification of discriminative plasma protein biomarkers for recent Mycobacterium tuberculosis infection: a pilot data-independent acquisition mass spectrometry-based proteomics study","volume":"26","author":"Han","year":"","journal-title":"BMC Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2003492","DOI":"10.1183\/13993003.03492-2020","article-title":"Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model","volume":"58","author":"Heyckendorf","year":"2021","journal-title":"Eur. Respir. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1087010","DOI":"10.3389\/fimmu.2022.1087010","article-title":"Single-cell profiling reveals distinct subsets of CD14+ monocytes drive blood immune signatures of active tuberculosis","volume":"13","author":"Hillman","year":"2023","journal-title":"Front. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5536","DOI":"10.1016\/j.cell.2023.11.002","article-title":"Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis","volume":"186","author":"Kotov","year":"2023","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2350666","DOI":"10.1002\/eji.202350666","article-title":"Neutrophil-plasmacytoid dendritic cell interaction leads to production of type I IFN in response to Mycobacterium tuberculosis","volume":"54","author":"Lee","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3390\/pathogens15050489","article-title":"RISK6 as a translational host transcriptomic signature for tuberculosis diagnosis, treatment monitoring, and risk stratification","volume":"15","author":"Mamudi","year":"2026","journal-title":"Pathogens"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e783","DOI":"10.1016\/S2214-109X(24)00029-9","article-title":"Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study","volume":"12","author":"Mann","year":"2024","journal-title":"Lancet Glob. Health"},{"key":"B22","doi-asserted-by":"publisher","first-page":"101153","DOI":"10.1016\/j.lanmic.2025.101153","article-title":"Blood RNA biomarkers and C-reactive protein for triage of adult patients with tuberculosis lymphadenitis and pericarditis in South Africa: a single-centre, prospective, observational, diagnostic accuracy study","volume":"6","author":"Mann","year":"2025","journal-title":"Lancet Microbe"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e841","DOI":"10.1016\/S2214-109X(21)00045-0","article-title":"Validation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study","volume":"9","author":"Mendelsohn","year":"2021","journal-title":"Lancet Glob. Health"},{"key":"B24","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s43856-022-00086-8","article-title":"Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR","volume":"2","author":"Mendelsohn","year":"2022","journal-title":"Commun. Med. (Lond)."},{"key":"B25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.12688\/gatesopenres.14452.2","article-title":"Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV","volume":"7","author":"Mendelsohn","year":"2023","journal-title":"Gates Open Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1355","DOI":"10.1093\/infdis\/jiae237","article-title":"Transcriptomic signatures of progression to tuberculosis disease among close contacts in Brazil","volume":"230","author":"Mendelsohn","year":"2024","journal-title":"J. Infect. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0237574","DOI":"10.1371\/journal.pone.0237574","article-title":"Performance of diagnostic and predictive host blood transcriptomic signatures for tuberculosis disease: a systematic review and meta-analysis","volume":"15","author":"Mulenga","year":"2020","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1164\/rccm.202103-0548OC","article-title":"Longitudinal dynamics of a blood transcriptomic signature of tuberculosis","volume":"204","author":"Mulenga","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2400153","DOI":"10.1183\/13993003.00153-2024","article-title":"Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study","volume":"64","author":"Muwanga","year":"2024","journal-title":"Eur. Respir. J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"20640","DOI":"10.1038\/s41598-022-25236-9","article-title":"Plasma host protein signatures correlating with Mycobacterium tuberculosis activity prior to and during antituberculosis treatment","volume":"12","author":"Ndiaye","year":"2022","journal-title":"Sci. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e14088","DOI":"10.15252\/emmm.202114088","article-title":"Diagnostic biomarkers for active tuberculosis: progress and challenges","volume":"14","author":"Nogueira","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"596173","DOI":"10.3389\/fimmu.2020.596173","article-title":"The peripheral blood transcriptome is correlated with PET measures of lung inflammation during successful tuberculosis treatment","volume":"11","author":"Odia","year":"2021","journal-title":"Front. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1546770","DOI":"10.3389\/fmicb.2025.1546770","article-title":"An integrative and comprehensive analysis of blood transcriptomic biomarkers for tuberculosis","volume":"16","author":"Omrani","year":"2025","journal-title":"Front. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8629","DOI":"10.1038\/s41598-020-65043-8","article-title":"RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response","volume":"10","author":"Penn-Nicholson","year":"2020","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1093\/infdis\/jiae365","article-title":"Plasma immune biomarkers predictive of progression to active tuberculosis in household contacts of patients with tuberculosis","volume":"231","author":"Rajamanickam","year":"2025","journal-title":"J. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"120","DOI":"10.20411\/pai.v10i1.770","article-title":"The TB27 transcriptomic model for predicting Mycobacterium tuberculosis culture conversion","volume":"10","author":"Reimann","year":"2025","journal-title":"Pathog. Immun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2400479","DOI":"10.1183\/13993003.00479-2024","article-title":"Detection of M. tuberculosis DNA in TB contacts' PBMC does not associate with blood RNA signatures for incipient tuberculosis","volume":"64","author":"Rosenheim","year":"2024","journal-title":"Eur. Respir. J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e173273","DOI":"10.1172\/jci.insight.173273","article-title":"Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers","volume":"9","author":"Schiff","year":"2024","journal-title":"JCI Insight"},{"key":"B39","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S1473-3099(20)30914-2","article-title":"Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial","volume":"21","author":"Scriba","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1624072","DOI":"10.3389\/fimmu.2025.1624072","article-title":"Single-cell transcriptomic profiling reveals a novel signature of necrotizing granulomatous lesions in the lungs of Mycobacterium tuberculosis-infected C3HeB\/FeJ mice","volume":"16","author":"Seto","year":"2025","journal-title":"Front. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"626049","DOI":"10.3389\/fimmu.2020.626049","article-title":"Host blood RNA transcript and protein signatures for sputum-independent diagnostics of tuberculosis in adults","volume":"11","author":"Sivakumaran","year":"2021","journal-title":"Front. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1051963","DOI":"10.3389\/fimmu.2022.1051963","article-title":"Host blood-based biosignatures for subclinical TB and incipient TB: a prospective study of adult TB household contacts in Southern India","volume":"13","author":"Sivakumaran","year":"2023","journal-title":"Front. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12916-021-02127-w","article-title":"The impact of blood transcriptomic biomarker targeted tuberculosis preventive therapy: a mathematical modelling study","volume":"19","author":"Sumner","year":"2021","journal-title":"BMC Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1021\/acsinfecdis.4c00374","article-title":"Cost-effective whole transcriptome sequencing landscape and diagnostic potential biomarkers in active tuberculosis","volume":"10","author":"Sun","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e20210915","DOI":"10.1084\/jem.20210915","article-title":"Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis","volume":"218","author":"Tabone","year":"2021","journal-title":"J. Exp. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2401669","DOI":"10.1183\/13993003.01669-2024","article-title":"Blood RNA signatures for 8-week sputum tuberculosis culture sterilisation: how close are we?","volume":"64","author":"Thu","year":"2024","journal-title":"Eur. Respir. J."},{"key":"B47","volume-title":"Global Tuberculosis Report 2025","year":"2025"},{"key":"B48","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s12915-026-02585-9","article-title":"PTBD: a machine learning-based non-invasive diagnostic model for pulmonary tuberculosis using large-scale blood transcriptomes","volume":"24","author":"Wu","year":"","journal-title":"BMC Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"115178","DOI":"10.1016\/j.isci.2026.115178","article-title":"Multidimensional cfRNA response modeling identifies a 5-gene pair signature for high-robust pulmonary tuberculosis diagnosis","volume":"29","author":"Wu","year":"","journal-title":"iScience"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e0185921","DOI":"10.1128\/jcm.01859-21","article-title":"Biomarkers that correlate with active pulmonary tuberculosis treatment response and disease activity: a systematic review and meta-analysis","volume":"60","author":"Zimmer","year":"2022","journal-title":"J. Clin. Microbiol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1916291\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:53:52Z","timestamp":1787554432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1916291\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":50,"alternative-id":["10.3389\/fcell.2026.1916291"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1916291","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"article-number":"1916291"}}