TIGIT blockade improves anti-Mycobacterium tuberculosis immunity.

Area of Science:

• Immunology
• Infectious Diseases
• Tuberculosis Research

Background:

• Immune checkpoint blockade shows therapeutic benefits in cancer but its role in infectious diseases is unclear.
• T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is an immune checkpoint receptor expressed on T cells.
• Active Mycobacterium tuberculosis infection impacts T cell immunity, but the role of TIGIT is not well understood.

Purpose of the Study:

• To investigate if blocking TIGIT enhances T cell immunity in active tuberculosis.
• To assess TIGIT expression in tuberculosis patients and its correlation with disease severity.
• To evaluate the therapeutic potential of TIGIT blockade in tuberculosis.

Main Methods:

• Assessed TIGIT expression in peripheral blood and lung lesions of tuberculosis patients.
• Analyzed the functional status of TIGIT+ and TIGIT-CD8+ T cell subsets using flow cytometry and transcriptome analysis.
• Investigated the effect of TIGIT blockade on CD8+ T cell function in vitro and bacterial load in a tuberculosis mouse model.

Main Results:

• TIGIT was significantly upregulated on CD8+ T cells in active tuberculosis patients, correlating with disease severity.
• TIGIT expression was higher in pulmonary tuberculosis lesions compared to other infections.
• TIGIT blockade enhanced CD8+ T cell effector functions and reduced bacterial burden in mice.

Conclusions:

• Activated CD8+ T cells express TIGIT in active tuberculosis, limiting T cell immunity.
• TIGIT blockade enhances CD8+ T cell function and promotes Mycobacterium tuberculosis clearance.
• TIGIT blockade represents a potential novel therapeutic strategy for tuberculosis.