Toll-like Receptors and Periodontitis: Current Insights into Immune Dynamics and Translational Therapeutics

Trends in Immunotherapy

Review Article

Toll-like Receptors and Periodontitis: Current Insights into Immune Dynamics and Translational Therapeutics

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https://doi.org/10.54963/ti.v10i1.1428
Liew, F. F., Tan, S. H., Sengupta, P., & Dutta, S. (2026). Toll-like Receptors and Periodontitis: Current Insights into Immune Dynamics and Translational Therapeutics. Trends in Immunotherapy, 10(1), 13–42. https://doi.org/10.54963/ti.v10i1.1428
Volume 10, Issue 1 (March 2026): In Progress
Copyright (c) 2026 Fong Fong Liew, Soon Hao Tan, Pallav Sengupta, Sulagna Dutta
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Authors

  • Fong Fong Liew

    Department of Preclinical Sciences, Faculty of Dentistry, MAHSA University, Bandar Saujana Putra, 42610 Jenjarom, Selangor, Malaysia
  • Soon Hao Tan

    Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
  • Pallav Sengupta

    Department of Biomedical Sciences, College of Medicine, Gulf Medical University, 4184 Ajman, United Arab Emirates
  • Sulagna Dutta

    Basic Medical Sciences Department, College of Medicine, Ajman University, 4184 Ajman, United Arab Emirates

Received: 22 July 2025; Revised: 31 July 2025; Accepted: 14 August 2025; Published: 7 January 2026

Periodontitis is a common and persistent inflammatory disease resulting from a sophisticated relationship between oral bacteria and the body's immune system. Toll-like receptors (TLRs) act as crucial sensors within the immune response, playing a fundamental role in the disease's initiation and progression. This review examines periodontitis, highlighting the limited understanding of TLR activation mechanisms and the therapeutic potential of TLR inhibitors. The discussion begins with a definition of TLRs, outlining their characteristics, types, distribution, and activation mechanisms. It then details the manifestation of TLRs in periodontitis, including alterations during inflammation and their correlation with disease severity. TLR activity is influenced not only by microbial stimuli but also by epigenetic factors and miRNAs, which mediate gene expression changes linked to inflammation. Various miRNAs have been shown to regulate TLR signaling pathways, thereby modulating the inflammatory response in periodontal tissues. Additionally, epigenetic modifications further complicate the landscape of immune regulation in periodontitis, affecting TLR expression and function. This interplay between TLRs, miRNAs, and epigenetic changes underscores the systemic implications of periodontal disease, contributing to broader health issues. Consequently, the review explores innovative strategies to modulate TLR signaling and discusses future challenges in TLR research in relation to periodontitis treatment. In summary, a more profound understanding of TLR-driven immune responses, along with the regulatory roles of miRNAs and epigenetic factors, is essential for developing targeted therapies and advancing treatment options for periodontitis.

Keywords:

Inflammation Pathogen-Associated Molecular Patterns Periodontitis Toll-Like Receptors TLR2 TLR4

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