The Role of Toll-Like Receptor-2 in the Pathogenesis of Pulmonary Tuberculosis

Sudarto, Sudarto and Hafy, Zen and Saleh, Irfan and Liberty, Iche Andriyani and Ahmad, Zen and Lubis, Fadhyl Zuhri and Hu, Owen and Salutondok, Welly (2025) The Role of Toll-Like Receptor-2 in the Pathogenesis of Pulmonary Tuberculosis. Indonesian Journal of Global Health Research, 7 (3). pp. 1089-1100. ISSN 2715-1972

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Abstract

Pulmonary tuberculosis (PTB), primarily caused by Mycobacterium tuberculosis (M.tb), remains a major global health burden. Toll-like receptor 2 (TLR-2), a critical component of the innate immune system, plays a key role in the host-pathogen interaction by recognizing specific components of the mycobacterial cell wall and initiating downstream inflammatory pathways. However, the dual role of TLR-2 in both protective immunity and immune evasion by M.tb contributes to the complexity of TB pathogenesis. This study aims to investigate the role of Toll-Like Receptor-2 (TLR-2) in the pathogenesis of pulmonary tuberculosis, including its immunological mechanisms, relationships with disease severity, and the potential of TLR-2 as a diagnostic and therapeutic target. This literature review systematically analyzed molecular mechanisms involving TLR-2 signaling in pulmonary TB using peer-reviewed primary and secondary sources from experimental and clinical studies. Emphasis was placed on signal transduction (NF-κB and MAPK), cytokine profiles, antigen presentation, and the impact of TLR-2 gene polymorphisms on TB susceptibility. Activation of TLR-2 through ligands such as lipoproteins, lipoarabinomannan (LAM), and PE/PPE proteins initiates immune responses via MyD88-dependent pathways, leading to the release of proinflammatory cytokines (TNF-α, IL-6, IL-12). TLR-2 also enhances the function of macrophages and dendritic cells, promoting Th1-mediated immunity. However, chronic or excessive stimulation of TLR-2 can suppress antigen processing, promote IL-10 expression, inhibit phagolysosome fusion, and facilitate M. tb survival within host macrophages. Polymorphisms in the TLR-2 gene (e.g., rs3804099) have been associated with increased susceptibility and variable clinical outcomes in PTB. TLR-2 plays a paradoxical role in pulmonary tuberculosis by mediating both protective immunity and facilitating immune evasion by M.tb. Understanding the balance of TLR-2 signaling and genetic variation is crucial for developing immunomodulatory therapies and personalized interventions in TB management.

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