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Toll-Like Receptors (TLRs) in Health and Disease: An Overview

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Toll-like Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 276))

Abstract

Toll-like receptors were discovered as proteins playing a crucial role in the dorsoventral patterning during embryonic development in the Drosophila melanogaster (D. melanogaster) almost 40 years ago. Subsequently, further research also showed a role of the Toll protein or Toll receptor in the recognition of Gram-positive bacterial and fungal pathogens infecting D. melanogaster. In 1997, the human homolog was reported and the receptor was named the Toll-like receptor 4 (TLR4) that recognizes lipopolysaccharide (LPS) of the Gram-negative bacteria as a pathogen-associated molecular pattern (PAMP). Identification of TLR4 in humans filled the long existing gap in the field of infection and immunity, addressing the mystery surrounding the recognition of foreign pathogens/microbes by the immune system. It is now known that mammals (mice and humans) express 13 different TLRs that are expressed on the outer cell membrane or intracellularly, and which recognize different PAMPs or microbe-associated molecular patterns (MAMPs) and death/damage-associated molecular patterns (DAMPs) to initiate the protective immune response. However, their dysregulation generates profound and prolonged pro-inflammatory immune responses responsible for different inflammatory and immune-mediated diseases. This chapter provides an overview of TLRs in the control of the immune response, their association with different diseases, including TLR single nucleotide polymorphisms (SNPs), interactions with microRNAs (miRs), use in drug development and vaccine design, and expansion in neurosciences to include pain, addiction, metabolism, reproduction, and wound healing.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA

    Vijay Kumar

  2. Drexel University College of Medicine, Philadelphia, PA, USA

    James E. Barrett

  3. Department of Neural Sciences, Centre for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    James E. Barrett

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  1. Vijay Kumar
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Correspondence to Vijay Kumar or James E. Barrett .

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  1. Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center (DUMC), Durham, NC, USA

    Vijay Kumar

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Kumar, V., Barrett, J.E. (2022). Toll-Like Receptors (TLRs) in Health and Disease: An Overview. In: Kumar, V. (eds) Toll-like Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 276. Springer, Cham. https://doi.org/10.1007/164_2021_568

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