scholarly journals Molecular Mechanisms of the Toll-Like Receptor, STING, MAVS, Inflammasome, and Interferon Pathways

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Nathan P. Manes ◽  
Aleksandra Nita-Lazar
Keyword(s):  
Pattern Recognition ◽  
Molecular Interaction ◽  
Molecular Mechanisms ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Front Line ◽  
Pathway Models

Pattern recognition receptors (PRRs) form the front line of defense against pathogens. Many of the molecular mechanisms that facilitate PRR signaling have been characterized in detail, which is critical for the development of accurate PRR pathway models at the molecular interaction level.

Pattern recognition receptor-mediated innate immune responses in seminal vesicle epithelial cell and their impacts on cellular function†

2019 ◽  
Vol 101 (4) ◽  
pp. 733-747 ◽  
Author(s):  
Maolei Gong ◽  
Fei Wang ◽  
Weihua Liu ◽  
Ran Chen ◽  
Han Wu ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Pattern Recognition Receptors ◽  
Seminal Vesicles ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Recognition Receptor

Abstract The seminal vesicles can be infected by microorganisms, thereby resulting in vesiculitis and impairment in male fertility. Innate immune responses in seminal vesicles cells to microbial infections, which facilitate vesiculitis, have yet to be investigated. The present study aims to elucidate pattern recognition receptor–mediated innate immune responses in seminal vesicles epithelial cells. Various pattern recognition receptors, including Toll-like receptor 3, Toll-like receptor 4, cytosolic ribonucleic acid, and deoxyribonucleic acid sensors, are abundantly expressed in seminal vesicles epithelial cells. These pattern recognition receptors can recognize their respective ligands, thus activating nuclear factor kappa B and interferon regulatory factor 3. The pattern recognition receptor signaling induces expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (Tnfa) and interleukin 6 (Il6), chemokines monocyte chemoattractant protein-1 (Mcp1) and C–X–C motif chemokine 10 (Cxcl10), and type 1 interferons Ifna and Ifnb. Moreover, pattern recognition receptor-mediated innate immune responses up-regulated the expression of microsomal prostaglandin E synthase and cyclooxygenase 2, but they down-regulated semenogelin-1 expression. These results provide novel insights into the mechanism underlying vesiculitis and its impact on the functions of the seminal vesicles.

scholarly journals Role of Toll-Like Receptors in Pathogen Recognition

2003 ◽  
Vol 16 (4) ◽  
pp. 637-646 ◽  
Author(s):  
S. Janssens ◽  
R. Beyaert
Keyword(s):  
Pattern Recognition ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Pattern Recognition Receptors ◽  
Molecular Structures ◽  
Toll Like Receptors ◽  
Endogenous Ligands ◽  
Molecular Pattern ◽  
Proteolytic Cascade

SUMMARY The innate immune system relies on a vast array of non-clonally expressed pattern recognition receptors for the detection of pathogens. Pattern recognition receptors bind conserved molecular structures shared by large groups of pathogens, termed pathogen-associated molecular patterns. The Toll-like receptors (TLRs) are a recently discovered family of pattern recognition receptors which show homology with the Drosophila Toll protein and the human interleukin-1 receptor family. Engagement of different TLRs can induce overlapping yet distinct patterns of gene expression that contribute to an inflammatory response. The TLR family is characterized by the presence of leucine-rich repeats and a Toll/interleukin-1 receptor-like domain, which mediate ligand binding and interaction with intracellular signaling proteins, respectively. Most TLR ligands identified so far are conserved microbial products which signal the presence of an infection, but evidence for some endogenous ligands that might signal other danger conditions has also been obtained. Molecular mechanisms for pathogen-associated molecular pattern recognition still remain elusive but seem to be more complicated than initially anticipated. In most cases, direct binding of microbial ligands to TLRs still has to be demonstrated. Moreover, Drosophila TLRs bind endogenous ligands, generated through a proteolytic cascade in response to an infection. In the case of endotoxin, recognition involves a complex of TLR4 and a number of other proteins. Moreover, TLR heterodimerization further extends the spectrum of ligands and modulates the response towards specific ligands. The fact that TLR expression is regulated in both a cell type- and stimulus-dependent fashion further contributes to the complexity.

Stimulation of innate immune responses by malarial glycosylphosphatidylinositol via pattern recognition receptors

Parasitology ◽  
2005 ◽  
Vol 130 (S1) ◽  
pp. S45-S62 ◽  
Author(s):  
T. NEBL ◽  
M. J. DE VEER ◽  
L. SCHOFIELD
Keyword(s):  
Pattern Recognition ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
Pattern Recognition Receptors ◽  
Innate Immune ◽  
Proinflammatory Responses ◽  
Cellular Immune

The glycosylphosphatidylinositol (GPI) anchor ofPlasmodium falciparumis thought to function as a critical toxin that contributes to severe malarial pathogenesis by eliciting the production of proinflammatory responses by the innate immune system of mammalian hosts. Analysis of the fine structure ofP. falciparumGPI suggests a requirement for the presence of both core glycan and lipid moieties in the recognition and signalling of parasite glycolipids by host immune cells. It has been demonstrated that GPI anchors of various parasitic protozoa can mediate cellular immune responses via members of the Toll-like family of pattern recognition receptors (TLRs). Recent studies indicate that GPI anchors ofP. falciparumand other protozoa are preferentially recognized by TLR-2, involving the MyD88-dependent activation of specific signalling pathways that mediate the production of proinflammatory cytokines and nitric oxide from host macrophagesin vitro. However, the contribution of malaria GPI toxin to severe disease syndromes and the role of specific TLRs or other pattern recognition receptors in innate immunityin vivois only just beginning to be characterized. A better understanding of the molecular mechanisms underlying severe malarial pathogenesis may yet lead to substantial new insights with important implications for the development of novel therapeutics for malaria treatment.

scholarly journals Extracellular RNA Sensing by Pattern Recognition Receptors

2018 ◽  
Vol 10 (5-6) ◽  
pp. 398-406 ◽  
Author(s):  
Megumi Tatematsu ◽  
Kenji Funami ◽  
Tsukasa Seya ◽  
Misako Matsumoto
Keyword(s):  
Pattern Recognition ◽  
Molecular Mechanisms ◽  
Pattern Recognition Receptors ◽  
Endocytic Pathway ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Extracellular Rna ◽  
A Genome ◽  
Wide Range

RNA works as a genome and messenger in RNA viruses, and it sends messages in most of the creatures of the Earth, including viruses, bacteria, fungi, plants, and animals. The human innate immune system has evolved to detect single- and double-stranded RNA molecules from microbes by pattern recognition receptors and induce defense reactions against infections such as the production of type I interferons and inflammatory cytokines. To avoid cytokine toxicity causing chronic inflammation or autoimmunity by sensing self-RNA, the activation of RNA sensors is strictly regulated. All of the Toll-like receptors that recognize RNA are localized to endosomes/lysosomes, which require internalization of RNA for sensing through an endocytic pathway. RIG-I-like receptors sense RNA in cytosol. These receptors are expressed in a cell type-specific fashion, enabling sensing of RNA for a wide range of microbial invasions. At the same time, both endosomal and cytoplasmic receptors have strategies to respond only to RNA of pathogenic microorganisms or dying cells. RNA are potential vaccine adjuvants for immune enhancement against cancer and provide a benefit for vaccinations. Understanding the detailed molecular mechanisms of the RNA-sensing system will help us to broaden the clinical utility of RNA adjuvants for patients with incurable diseases.

scholarly journals Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna E. Spiering ◽  
Teun J. de Vries
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Pattern Recognition Receptors ◽  
Dose Effect ◽  
Toll Like Receptor ◽  
Novel Studies ◽  
Gene Dose ◽  
Male Sex ◽  
Tlr7 Stimulation

A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.

scholarly journals Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta

Immunology ◽  
2002 ◽  
Vol 107 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Ulrika Holmlund ◽  
Gvido Cebers ◽  
Agneta R. Dahlfors ◽  
Bengt Sandstedt ◽  
Katarina Bremme ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Human Placenta ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Toll Like Receptor 2

scholarly journals Nucleotide Oligomerization Domain 2 (Nod2) Is Not Involved in the Pattern Recognition of Candida albicans

2006 ◽  
Vol 13 (3) ◽  
pp. 423-425 ◽  
Author(s):  
Chantal A. A. van der Graaf ◽  
Mihai G. Netea ◽  
Barbara Franke ◽  
Stephen E. Girardin ◽  
Jos W. M. van der Meer ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Candida Albicans ◽  
Cytokine Production ◽  
Nucleotide Binding ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Nucleotide Oligomerization ◽  
Toll Like Receptor 2 ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

ABSTRACT Nucleotide-binding oligomerization domain 2 (Nod2) pathways are known to interact with Toll-like receptor 2 (TLR2) and TLR4, which are pattern recognition receptors for Candida albicans. We observed that the prevalence of Nod2 polymorphisms was not increased in patients with Candida infections. Candida-induced cytokine production in individuals with Nod2 polymorphisms was unaffected. We conclude that Nod2 is unlikely to play an important role in the recognition of Candida albicans.

Sign in / Sign up

Export Citation Format

Share Document