Abstract
Background/Aim Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system to each other. The TLRs are activated through binding to damage/danger-associated molecular patterns (DAMPs), microbial/microbe-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). The immunogenetic molecules of TLRs have their own functions, structures, coreceptors, and ligands which make them unique. These properties of TLRs give us an opportunity to find out how we can employ this knowledge for ligand-drug discovery strategies to control TLRs functions and contribution, signaling pathways, and indirect activities. Hence, the authors of this paper have a deep observation on the molecular and structural biology of human TLRs (hTLRs). Methods and Materials To prepare this paper and fulfill our goals, different search engines (e.g., GOOGLE SCHOLAR), Databases (e.g., MEDLINE), and websites (e.g., SCOPUS) were recruited to search and find effective papers and investigations. To reach this purpose, we tried with papers published in the English language with no limitation in time. The iCite bibliometrics was exploited to check the quality of the collected publications. Results Each TLR molecule has its own molecular and structural biology, coreceptor(s), and abilities which make them unique or a complementary portion of the others. These immunogenetic molecules have remarkable roles and are much more important in different sections of immune and nonimmune systems rather than that we understand to date. Conclusion TLRs are suitable targets for ligand-drug discovery strategies to establish new therapeutics in the fields of infectious and autoimmune diseases, cancers, and other inflammatory diseases and disorders.
Highlights
The mathematical and computational immunology shows the dynamics, kinetics, molecular and structural models, and characteristics of immune molecules, cells, signaling pathways and responses, and their synergistic mechanisms and cross-talks
Effective knowledge about Toll-like receptors (TLRs) provides us a brilliant promise to recognize these immune glycoproteins as effective immunogenetic targets for ligand-drug discovery strategies to establish new therapeutics in the fields of infectious diseases, cancers, and autoimmune diseases
As the reported results show, the TLR agonists as a new class of immunomodulators offer an effective protection with a significant long-activity against a wide range of microbe-associated molecular patterns (MAMPs)/ MAMPs through promoting the innate immune system activities
Summary
The mathematical and computational immunology shows the dynamics, kinetics, molecular and structural models, and characteristics of immune molecules, cells, signaling pathways and responses, and their synergistic mechanisms and cross-talks. The cGAS-STING signaling pathway act as cytosolic PRRs to identify intracellular double-stranded DNA (dsDNA) molecules and inducing the expression of type I IFN in the presence of dsDNA viruses, hostoriginated self dsDNAs, and the retroviruses of human immunodeficiency virus-1 (HIV-1) and HIV-2. Based on TLR molecules amino acid sequences, the family of TLRs in human (hTLRs) consists of five members such as TLR1, TLR3, TLR4, TLR5, and TLR7 (Table 1) and in mice is comprised of seven members including TLR1, TLR3, TLR4, TLR5, TLR7, TLR11, and TLR13 [7, 23, 26, 28, 50, 51] These biosensors have their specific molecular structures, characteristics, and abilities and are involved in infectious diseases, autoimmune diseases, and even cancers. Heterodimers peptides, TLR2, CD36, of TLR2- oxidized low- Diacyl lipoproteins, TLR6
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