Recent Advances in Studying Toll-like Receptors with the Use of Computational Methods

Bzówka, Maria; Bagrowska, Weronika; Góra, Artur

doi:10.1021/acs.jcim.3c00419

Cited by 5 publications

(4 citation statements)

References 120 publications

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“…The horseshoe-like structure LRR and TLRs interact with their respective PAMPs or DAMPs as a homo- or heterodimer in addition to an accessory or co-receptor molecule to initiate TLR-mediated immune responses ( Kawasaki and Kawai, 2014 ; Bzówka et al., 2023 ). The activation of signal transduction pathways linked to the activation of NF-kB, IRFs, or MAP kinases is initiated by TLRs upon recognition of PAMPs and DAMPs through the use of TIR domain-containing adaptor proteins such as myeloid differentiation primary response gene (MyD88), TIR domain-containing adaptor inducing interferon (IFN)β (TRIF), and TRIF related adaptor molecule (TRAM) ( Deguine and Barton, 2014 ; Ahmed et al., 2021 ).…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Moghaddam,

Behzadi,

Sedighian

et al. 2024

Front. Cell. Infect. Microbiol.

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Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host’s defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

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Section: Toll-like Receptorsmentioning

confidence: 99%

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Moghaddam,

Behzadi,

Sedighian

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Each of the ten functional TLRs (TLR1-10) in humans plays a pivotal role in detecting various dangers and pathogenassociated molecular patterns, including DAMPs, MAMPs, PAMPs, and XAMPs. These receptors share a common domain organization that includes an N-terminal domain with LRRs, a single TM, and a C-terminal cytoplasmic TIR domain [1,64].…”

Section: Recent Discoveries and Technological Advancementsmentioning

confidence: 99%

“…Humans possess ten functional TLRs (TLR1-10), each specializing in detecting different signals and pathogen-associated molecular patterns, including damage-associated molecular patterns (DAMPs), microbialassociated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). These receptors share a common structural organization, comprising an N-terminal domain with leucine-rich repeats (LRRs), a single transmembrane helix (TM), and a C-terminal cytoplasmic Toll-interleukin-1 receptor (TIR) domain [1]. The aim of this review is to delineate the multifaceted roles of TLRs within the scope of the innate immune system, elucidating their structural characteristics, signaling pathways, and implications in various diseases.…”

Section: Introduction 1overview Of Innate Immunity and Pattern Recogn...mentioning

confidence: 99%

Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications

Chen,

Wu,

2024

IJMS

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Toll-like receptors (TLRs) are vital components of the innate immune system, serving as the first line of defense against pathogens by recognizing a wide array of molecular patterns. This review summarizes the critical roles of TLRs in immune surveillance and disease pathogenesis, focusing on their structure, signaling pathways, and implications in various disorders. We discuss the molecular intricacies of TLRs, including their ligand specificity, signaling cascades, and the functional consequences of their activation. The involvement of TLRs in infectious diseases, autoimmunity, chronic inflammation, and cancer is explored, highlighting their potential as therapeutic targets. We also examine recent advancements in TLR research, such as the development of specific agonists and antagonists, and their application in immunotherapy and vaccine development. Furthermore, we address the challenges and controversies surrounding TLR research and outline future directions, including the integration of computational modeling and personalized medicine approaches. In conclusion, TLRs represent a promising frontier in medical research, with the potential to significantly impact the development of novel therapeutic strategies for a wide range of diseases.

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“…From the Protein Data Bank (PDB), [29] the X-Ray Diffraction structure of TLR-8 (PDB ID: 3W3G) with resolution 2.3 was obtained.The Cluspro server (https://cluspro.bu.edu/peptide/index.php) was used for docking analysis to make sure the created vaccine elicits an immunological response. [30][31] [32][33] [34] 2.10 Molecular dynamic simulation of docked complex:…”

Section: Estimating Different Properties Of the Constructed Vaccinesmentioning

confidence: 99%

Epitope-based Vaccine Design for California Encephalitis Virus(Cev) : a Computational Study Targeting Membrane Glycoproteins

Surendra,

Nelluri,

Male*

et al. 2024

Preprint

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California encephalitis is an uncommon viral brain infection that is caused by the California encephalitis virus (CEV).With encephalitis, the majority of patients experience full recovery with a mortality rate of less than 1%. A 20% or higher percentage of patients experience recurring seizures or behavioural issues. There is currently no vaccine or prescribed medication for California encephalitis, an infectious disease that is on the rise. Therefore, the development of a novel vaccination against CEV is imperative. The current study develops a vaccine based on many epitopes using immunoinformatic methods. B and T cell epitopes were predicted using the CEV membrane glycoprotein polyprotein as a target protein. The predicted T- and B-cell epitopes were then examined for conservancy, toxicity, allergenicity, and immunogenicity. HLA alleles were paired with screened epitopes to make sure they interacted to trigger an immune response. The best selected epitopes were used to create the vaccine. Studying the vaccine's physicochemical qualities and other features revealed its immunogenicity, stability, and safety. Afterwards, two Toll-like receptor-8 (TLR-8) was docked with the vaccination, and molecular dynamic simulations were examined. To ensure that the vaccine's codons would express themselves efficiently in a plasmid vector for in silico cloning tests, more codon adaptation of the vaccine sequence was carried out. It is predicted that the vaccine developed for this study will demonstrate its efficacy in controlling and preventing CEV .To make sure it's safe and effective, more in vivo and in vitro research needs to be done.

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Recent Advances in Studying Toll-like Receptors with the Use of Computational Methods

Cited by 5 publications

References 120 publications

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications

Epitope-based Vaccine Design for California Encephalitis Virus(Cev) : a Computational Study Targeting Membrane Glycoproteins

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