TIGIT blockade improves anti-Mycobacterium tuberculosis immunity

PMCID: PMC12173411

PMID: 40526725

DOI: 10.1371/journal.ppat.1013228

Journal: PLoS pathogens

Publication Date: 2025-6-17

Authors: Zhou J, Yang Q, Xu H, Chen H, Jiang N, et al.

Key Points

• TIGIT expression on CD8+ T cells is significantly elevated in active TB patients and correlates with disease severity
• TIGIT blockade reduced lung bacterial burden by approximately 10-fold in mouse models
• Targeting TIGIT may offer a new immunotherapeutic approach for tuberculosis treatment

Summary

This study investigated the role of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) in active tuberculosis (TB) infection, revealing a complex interaction between TIGIT expression and T cell immunity. Researchers found that TIGIT expression on CD8+ T cells was significantly upregulated in active TB patients, correlating positively with disease severity and showing a distinct activation profile different from traditional immune exhaustion.

The research demonstrated that TIGIT+ CD8+ T cells exhibited enhanced activation, increased cytokine production, and maintained robust effector functions. Critically, TIGIT blockade showed promising therapeutic potential, increasing the ability of CD8+ T cells to produce effector molecules and reducing bacterial load in both in vitro and mouse model experiments. These findings suggest that TIGIT blockade could represent a novel therapeutic strategy for managing tuberculosis infection.