Regulatory T Cell Dynamics in Mycobacterium Tuberculosis Infection

The immune response to Mycobacterium tuberculosis involves a delicate balance between protective inflammation and regulatory restraint. CD4+CD25+FoxP3+ regulatory T cells (Tregs) accumulate at sites of infection and in draining lymph nodes, where they limit excessive Th1- and Th17-mediated responses through inhibitory cytokines and checkpoint receptors. While this suppression protects host tissues, it also permits bacterial persistence and may contribute to latent infection. Signals from antigen‐presenting cells, including co‐signal pathways and inflammatory mediators, govern Treg induction, expansion and trafficking. Conversely, Treg attenuation has been shown in experimental models to enhance vaccine‐induced Th1 immunity and reduce bacterial load. Unravelling the phenotypic heterogeneity, migratory behaviour and functional plasticity of Tregs in tuberculosis holds promise for therapies that recalibrate host immunity to achieve bacterial clearance without exacerbating tissue damage.

Research from Nature Portfolio

One seminal study has defined how infected dendritic cells exploit sonic hedgehog signalling to orchestrate Treg expansion. Activation of the SHH–GLI1 axis in human dendritic cells drives cyclooxygenase-2–dependent prostaglandin E2 synthesis and upregulates programmed death-ligand 1. Concurrent downregulation of microRNAs targeting PD-L1 releases inhibitory checkpoints, creating a feed-forward loop that amplifies FoxP3+ Treg proliferation. Cross-talk with NOTCH1 pathways further refines this balance, revealing key molecular targets for disrupting pathogen-driven immune suppression.

Regulatory T Cell Dynamics in Mycobacterium Tuberculosis Infection publication trend

The graph below shows the total number of articles in regulatory t cell dynamics in mycobacterium tuberculosis infection across all publications each year (not limited to Nature Index journals).

Technical terms

Regulatory T cell (Treg): A subset of CD4+ T lymphocytes expressing FoxP3 that suppress immune responses to maintain tolerance and limit tissue damage.

Dendritic cell (DC): A professional antigen-presenting cell that processes antigens and provides costimulatory signals to initiate T cell activation.

Programmed death-ligand 1 (PD-L1): An inhibitory ligand on antigen-presenting cells or infected cells that engages PD-1 on T cells to attenuate immune activity.

BTLA/HVEM axis: A bidirectional cosignalling pathway involving B and T lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM) that regulates T cell activation and tolerance.

Sonic hedgehog (SHH) signalling: A conserved pathway that activates GLI transcription factors in antigen-presenting cells to modulate immune gene expression.

Prostaglandin E2 (PGE2): A lipid mediator produced by cyclooxygenase-2 that influences inflammation and promotes regulatory T cell expansion.

HLA-DR+ effector memory T cell: An activated CD4+ T cell expressing HLA-DR, marking immune activation and conferring resistance to regulatory suppression.

References

1. Distinct characteristics of BTLA/HVEM axis expression on Tregs and its impact on the expansion and attributes of Tregs in patients with active pulmonary tuberculosis. Frontiers in Cellular and Infection Microbiology (2024).
2. Regulatory T Cells in Mycobacterium tuberculosis Infection. Frontiers in Immunology (2019).
3. Mycobacteria-responsive sonic hedgehog signaling mediates programmed death-ligand 1- and prostaglandin E2-induced regulatory T cell expansion. Scientific Reports (2016).
4. Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis. PLOS Pathogens (2018).
5. Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis. PLOS ONE (2008).