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Recognition of microbe-associated molecular patterns by pattern recognition receptors
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Mammalian TLRs are type I transmembrane glycoproteins containing three common structural features: (1) a large extracellular domain with 19–25 consecutive leucine-rich repeats and one or two cysteine-rich regions, (2) a short transmembrane region, and (3) a highly conserved cytoplasmic domain (Figure 18.2). The extracellular domain is responsible for the recognition of PAMPs. The intracellular domain is highly homologous among the individual TLRs and contains a toll/interleukin-1 (IL-1) receptor (TIR) domain that mediates homodimeric or heterodimeric interactions between TLRs and initiates downstream signaling cascades, as discussed later. The TIR domain also is present in members of the closely related IL-1, IL-18, and IL-33 receptor families.
The immune response to fungal challenge
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Jeffery Hu, Jeffery J. Auletta
Toll-like receptors (TLRs) are type I integral membrane glycoproteins that belong to the Toll/interleukin-1 receptor (TIR) superfamily. The majority of TLRs are expressed on the cellular surface of immune cells (TLR 1, 2, 4–6, 11), while TLR 3, 7/8, and 9 are located in endosomal compartments [11]. TLRs use a conserved TIR domain in the cytosolic region to activate one of four adaptor proteins: the death-domain containing myeloid differentiation factor 88 (MyD88), TIRAP (TIR-adaptor containing adaptor protein, also known as MyD88-adaptor-like protein, MAL), TRIF (TIR-domain-containing adaptor protein inducing IFN-β), and TRAM (TRIF-adaptor molecule). Differential use of these adaptor proteins confers specificity to the TLR signaling pathways [12]. The majority of TLRs utilize MyD88 signal adaptor proteins to activate IRAKs and TRAF6, which ultimately activate NF-κB and mitogen-activated protein (MAP) kinases to synthesize inflammatory cytokines like IL-6 and TNF-α [13]. In contrast, TLR3-mediated signaling utilizes TRIF and IRF3 in producing type I interferons in a MyD88-independent manner [14]. TLR4 activation uniquely leads to both MyD88-dependent, early phase NF-κB transcription of proinflammatory cytokines (IL-1β, TNF-a, and IL-6) and MyD88-independent, late phase NF-κB transcription of IFN-β [13].
Bacterial Infections of the Oral Cavity
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
P. S. Manoharan, Praveen Rajesh
A report of three unrelated patients with interleukin receptor-associated kinase (IRAK) deficiency are resistant to pyogenic infections as opposed to healthy children who developed pyogenic infections (Picard et al., 2008). Toll interleukin receptor (TIR) mediates the recruitment of IRAK complex. This TIR-IRAK signal pathway is found to be important for immunity against some bacteria, but their role is negligible against other microorganisms. In a case control study of 150 patients who were pregnant or who were post-partum revealed that periodontal disease can be significant risk factor of preterm low birth-weight infants (Messinis et al., 2010).
The role of toll-like receptors (TLRs) in pan-cancer
Published in Annals of Medicine, 2022
Runzhi Huang, Zehui Sun, Shuyuan Xian, Dianwen Song, Zhengyan Chang, Penghui Yan, Jie Zhang, Huabin Yin, Zixuan Zheng, Peng Hu, Zhenyu Li, Dan Huang, Yihan Liu, Chenyang Jiang, Man Li, Siqi Li, Tong Meng, Daoke Yang, Zongqiang Huang
TLRs are a type of pattern-recognition receptors (PRRs) expressed in immune cells. They are best known for their pathogen defense function, which involves the recognition of damage-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide and flagellin, as well as RNA produced during virus replication. TLRs, on the other hand, are involved in the identification of several endogenous ligands, including damage-associated molecular patterns (DAMPs) generated by dying or wounded cells [1]. The human body contains a total of 13 TLR genes, of which TLR1-10 are protein-coding genes and TLR11-13 are pseudogenes. Notably, unlike the majority of other TLR genes, TLR8-AS1 is an RNA gene that belongs to the lncRNA class. The TLR family is categorised into two subgroups based on their position: TLR1, −2, −4, −5, −6, and −10 on the cell surface, and TLR3, −7, −8, and −9 on the intracellular endosome [2,3]. TLR contains both external and intracellular domains as a type I transmembrane glycoprotein. The former contains the leucine repeat sequence and detects ligands selectively. The latter contains the Toll-interleukin 1 (IL-1) receptor domain (TIR) and activates downstream signalling pathways such as the NF-B, p38-MAPK, and JUN-kinase [4].
Platycodin D inhibits MPP+-induced inflammatory response in BV-2 cells through the TLR4/MyD88/NF-κB signaling pathway
Published in Journal of Receptors and Signal Transduction, 2020
The TLR family consists of 10 members (TLR1–TLR10) and recognizes specific patterns of microbial components [18,19]. It has been established that TLRs play an essential role in the activation of innate immunity [20]. The activation of TLRs signaling pathways originates from the Toll/IL-1 receptor (TIR) domain, which is the cytoplasmic portion of TLRs [21]. Recent accumulating evidence has demonstrated that several TIR domain-containing adaptors, such as MyD88, TIRAP, and TRIF, are involved in the regulation of TLRs signaling pathways [20]. Among these, MyD88 has been found to possess the TIR domain in the C-terminal portion and a death domain in the N-terminal portion [22]. MyD88 is essential for the induction of inflammatory cytokines triggered by all TLRs. Upon stimulation, TLR-mediated MyD88-dependent pathway may lead to the activation of JNK and NF-κB.
Chicken toll-like receptors and their significance in immune response and disease resistance
Published in International Reviews of Immunology, 2019
Aamir Nawab, Lilong An, Jiang Wu, Guanghui Li, Wenchao Liu, Yi Zhao, Qimin Wu, Mei Xiao
All TLRs are type -1 transmembrane proteins characterized by several extracellular ligand-binding domains composed of 19–27 leucine-rich repeats (LRR) and an intracellular carboxy-terminal tail of TLRs consisting a highly conserved signaling region, which is called the Toll/interleukin receptor because of its homology with the interleukin-1 receptor signaling domain (TIR) [16, 17]. Generally, TIR domains are most conserved structure among TLRs family and, therefore, it is essential to trace the TLRs lineage in avian species [18]. TLRs have basic structural features and mild variations. Chicken TLR1LB and TLR7 structure have an additional transmembrane (TM) domain at the N- terminus while the majority of TLRs show a single TM domain between the extracellular and the intracellular domains [2, 11]. The predicted structure of TLR1LB is similar to TLR1LA except for the two missing LRRs at N-terminus. TLR15 has the rare feature of many LRRs domain towards the amino C-terminus of the receptor and limited at the N-terminus.