Role of Tumor Necrosis Factor in Tuberculosis

Area of Science:

• Immunology
• Infectious Diseases
• Molecular Biology

Background:

• Tumor necrosis factor (TNF) is a critical cytokine in host defense against Mycobacterium tuberculosis.
• TNF exhibits a dual role, essential for controlling latent infection but also implicated in immunopathology and tissue damage.

Purpose of the Study:

• To systematically review the molecular and cellular mechanisms of TNF action in tuberculosis (TB) pathogenesis.
• To analyze the balance between protective and pathological immune responses driven by TNF.
• To evaluate the impact of anti-TNF therapies on TB risk and host defense.

Main Methods:

• Systematic analysis of over 300 peer-reviewed studies (1980-2024) on TNF in TB.
• Review of TNF receptor signaling pathways and immune modulation.
• Integration of knowledge using schematic representations of TNF-driven immune dynamics.

Main Results:

• Different TNF inhibitors possess varying capacities to disrupt host defense mechanisms against TB.
• Monoclonal antibody TNF inhibitors are associated with a higher risk of TB reactivation compared to receptor-based agents.
• TNF influences granuloma stability and intracellular bacterial control.

Conclusions:

• Understanding TNF's pleiotropic functions in TB pathogenesis is vital for safe immunomodulatory strategies.
• Optimizing clinical management of patients at risk for latent TB reactivation requires careful consideration of TNF-targeting therapies.
• Differentiated risk profiles of TNF inhibitors necessitate tailored clinical approaches.