Citation

Toll‐like receptors (TLRs) were discovered almost three decades ago and their importance in the regulation of immune responses was immediately recognized. TLRs are pattern‐recognition receptors that can recognize microbial and viral products with specific structural features, which are classified as pathogen‐associated molecular patterns (PAMPs).[1] Each TLR can detect distinct PAMPs to initiate a series of signaling processes that constitute the first line of host defense.[2] Up to date, 13 TLRs have been discovered in mammalian cells.[1] However, only 10 TLRs (TLR1–TLR10) are expressed in hu- mans and only 12 TLRs (TLR1–TLR9 and TLR11–TLR13) are ex- pressed in mice.[3] TLRs are grouped into two major categories, endosomal (TLR9, TLR8, TLR7, and TLR3) and cell surface TLRs

(TLR10, TLR6, TLR5, TLR4, TLR2, and TLR1).[1] Endosomal TLRs are
mainly activated with nucleic acids. However, cell surface TLRs are activated with a variety of molecules including lipoproteins, lipopo- lysaccharide (LPS), and flagellin. After ligand attachment, TLRs di- merize and then activate intracellular cascade signaling. TLRs drives a cascade of signaling through the myeloid differentiation primary response 88 (MyD88)‐dependent pathway (in the case of all TLRs except for TLR3) or a Toll/interleukin receptor domain‐containing adapter‐inducing interferon β (TRIF)‐dependent pathway (in the case of TLR3 and TLR4).[4] MyD88 leads to early‐phase NF‐KB activation and mitogen‐activated protein kinases (MAPKs).[5] TRIF induces an alternative pathway responsible for the activation of MyD88‐independent signaling pathway, leading to late‐phase NF‐KB activation and interferon (IFN) regulatory factor (IRF) 3/7.[6,7]