Immunodiagnosis and Management of Tuberculosis Infection

Tuberculosis remains a leading cause of infectious mortality, driven in part by the challenge of detecting and managing the vast reservoir of latent infection. Immunodiagnosis relies chiefly on the tuberculin skin test and interferon-gamma release assays to identify individuals harbouring Mycobacterium tuberculosis without clinical disease. However, these tests have limitations in sensitivity, specificity and predictive value for progression to active disease. Advances in immunology have revealed novel biomarkers—ranging from cytokine signatures and T cell phenotypes to antibody profiles—that promise to refine risk stratification and guide preventive therapy. Management strategies now combine targeted screening of high-risk groups with chemoprophylaxis and bespoke host-directed therapies. A deeper understanding of innate and adaptive responses offers the prospect of more precise interventions to interrupt transmission and to move towards global elimination.

Research from Nature Portfolio

Recent studies have uncovered distinct immune signatures in individuals who, despite intense exposure to M. tuberculosis, neither convert conventional diagnostic tests nor develop disease. One investigation characterised a clonally expanded subset of CD4⁺ T cells in so-called “resisters,” demonstrating enrichment of TH17-like and regulatory programmes that correlate with bacterial control and absence of progression. Another analysis of heavily exposed household contacts in Indonesia identified BCG-associated trained immunity as a determinant of early clearance, marked by heightened innate cytokine production and inflammatory protein expression independently of specific antibody responses. Foundational work has also defined interferon-γ-independent markers of exposure in highly endemic settings, revealing class-switched IgG and IgM responses with enhanced Fc-glycosylation and avidity, thereby extending the diagnostic repertoire beyond classical cellular assays.

Immunodiagnosis and Management of Tuberculosis Infection publication trend

The graph below shows the total number of articles in immunodiagnosis and management of tuberculosis infection across all publications each year (not limited to Nature Index journals).

Technical terms

Tuberculin Skin Test (TST): An intradermal injection of purified protein derivative to elicit a delayed-type hypersensitivity reaction, used to infer prior sensitisation to M. tuberculosis.

Interferon-gamma Release Assay (IGRA): A blood test measuring release of interferon-γ by T cells after stimulation with M. tuberculosis-specific antigens, employed to detect latent infection.

Latent Tuberculosis Infection (LTBI): A state in which individuals harbour viable M. tuberculosis without clinical signs of active disease, carrying a risk of reactivation.

Trained Immunity: Epigenetic and metabolic reprogramming of innate immune cells after vaccination or infection, leading to enhanced nonspecific responses upon subsequent challenges.

Antigen-specific T cell: A lymphocyte that recognises a defined microbial peptide-MHC complex, pivotal for adaptive immunity and diagnostic assays.

References

1. Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis. Nature Immunology (2024).
2. Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia. Nature Communications (2025).
3. IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure. Nature Medicine (2019).
4. IFN-γ independent markers of Mycobacterium tuberculosis exposure among male South African gold miners. EBioMedicine (2023).
5. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis. EClinicalMedicine (2023).
6. Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018. Eurosurveillance (2024).