CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis

Area of Science:

• Immunology
• Infectious Diseases
• Molecular Biology

Background:

• Protective immunity against Mycobacterium tuberculosis relies on T cell and antigen-presenting cell interactions, modulated by cytokines.
• Costimulatory signals, involving complex receptor-ligand networks, significantly impact immune response quality and quantity.
• CD137 and CD137L are key molecules in immune regulation, prompting investigation into their role in human tuberculosis (TB).

Purpose of the Study:

• To investigate the function of CD137 and CD137L in the context of human tuberculosis.
• To elucidate how CD137:CD137L interactions influence innate and adaptive immune responses against Mycobacterium tuberculosis.

Main Methods:

• Analyzing CD137 and CD137L expression on monocytes, NK cells, and T lymphocytes from TB patients and healthy donors upon M. tuberculosis antigen stimulation.
• Utilizing CD137 pathway blockage to assess its impact on cytokine production (IFN-γ, TNF-α) by monocytes and NK cells.
• Evaluating the effects of CD137 blockage on CD8(+) T cell degranulation, cytokine production, and T-cell apoptosis.

Main Results:

• M. tuberculosis antigen stimulation upregulated CD137 and CD137L on monocytes and NK cells, and CD137 on T lymphocytes.
• CD137 pathway blockade enhanced IFN-γ and TNF-α production by monocytes and NK cells but decreased CD8(+) T cell degranulation and IFN-γ/TNF-α production.
• Inhibition of the CD137 pathway led to a significant increase in T-cell apoptosis.

Conclusions:

• CD137:CD137L interactions play a dual role in regulating host immune responses to Mycobacterium tuberculosis.
• The CD137 pathway modulates both innate (monocytes, NK cells) and adaptive (T cells) immunity during tuberculosis.
• Targeting the CD137:CD137L pathway may offer therapeutic strategies for tuberculosis, balancing innate and adaptive immune functions.