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Modulation of the Innate Immune Response by Targeting Toll-like Receptors: A Perspective on Their Agonists and
Stefano Federico1, Luca Pozzetti1, Alessandro Papa1
1Department of Biotechnology, Chemistry and Pharmacy, Department of Excellence 2018-2022, University of Siena, via Aldo Moro 2, 53100, Siena, Italy.
Abstract:
Toll-like receptors (TLRs) are a class of proteins that recognize pathogen-associated molecular patterns (PAMPs) and damaged-associated molecular patterns (DAMPs), and they are involved in the regulation of innate immune system. These transmembrane receptors, localized at the cellular or endosomal membrane, trigger inflammatory processes through either myeloid differentiation primary response 88 (MyD88) or TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathways. In the last decades, extensive research has been performed on TLR modulators and their therapeutic implication under several pathological conditions, spanning from infections to cancer, from metabolic disorders to neurodegeneration and autoimmune diseases. This Perspective will highlight the recent discoveries in this field, emphasizing the role of TLRs in different diseases and the therapeutic effect of their natural and synthetic modulators, and it will discuss insights for the future exploitation of TLR modulators in human health.
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