Immunotherapeutic Strategies in Tuberculosis Management

Despite the availability of antibiotic regimens, tuberculosis (TB) remains a leading cause of infectious mortality worldwide, exacerbated by rising rates of drug resistance. Immunotherapeutic strategies seek to augment or redirect the host immune response to improve clearance of Mycobacterium tuberculosis (M.tb) and prevent relapse. Approaches include host-directed therapies that modulate inflammatory pathways, small-molecule inhibitors of immunosuppressive enzymes, cytokine or checkpoint-blockade therapies to invigorate T cell responses, and vaccine adjuncts designed to generate durable memory populations. Central to these efforts are interventions that promote autophagy within infected macrophages, bolster Th1 and Th17 effector functions, and enrich lung-resident memory T cells capable of rapid local recall. Advances in understanding M.tb’s immune evasion—such as manipulation of epigenetic regulators—have stimulated the development of agents targeting host factors rather than bacterial enzymes, with the potential to synergise with standard antimicrobials. Immunotherapeutic strategies carry particular promise for multidrug-resistant TB, for which conventional chemotherapy alone often fails to achieve sterilising cure.

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Immunotherapeutic Strategies in Tuberculosis Management publication trend

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

Technical terms

Host-directed therapy: Intervention targeting host immune or metabolic pathways to enhance antimicrobial defence rather than directly attacking the pathogen.

Autophagy: Cellular process that delivers cytoplasmic material, including intracellular pathogens, to lysosomes for degradation, thereby aiding pathogen clearance.

Th1/Th17 cells: Subsets of CD4+ T helper cells that produce interferon-γ (Th1) or interleukin-17 (Th17), critical for controlling M.tb through macrophage activation and mucosal immunity.

Tissue-resident memory T cells (TRM): Long-lived memory T cells residing in non-lymphoid tissues, providing rapid local immune recall upon reinfection.

Epigenetic modulator: Protein or enzyme, such as a histone deacetylase, that alters chromatin structure and gene expression, affecting immune cell activation and differentiation.

References

1. Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention. MedComm (2024).
2. Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis. PLOS Pathogens (2023).
3. Host Sirtuin 2 as an immunotherapeutic target against tuberculosis. eLife (2020).