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.

Inhibitory pattern recognition receptors

2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Matevž Rumpret ◽  
Helen J. von Richthofen ◽  
Victor Peperzak ◽  
Linde Meyaard
Keyword(s):  
Pattern Recognition ◽  
Cell Death ◽  
Immune System ◽  
Immune Responses ◽  
Pattern Recognition Receptors ◽  
Inhibitory Receptors ◽  
Danger Signals ◽  
Molecular Pattern ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pathogen- and damage-associated molecular patterns are sensed by the immune system’s pattern recognition receptors (PRRs) upon contact with a microbe or damaged tissue. In situations such as contact with commensals or during physiological cell death, the immune system should not respond to these patterns. Hence, immune responses need to be context dependent, but it is not clear how context for molecular pattern recognition is provided. We discuss inhibitory receptors as potential counterparts to activating pattern recognition receptors. We propose a group of inhibitory pattern recognition receptors (iPRRs) that recognize endogenous and microbial patterns associated with danger, homeostasis, or both. We propose that recognition of molecular patterns by iPRRs provides context, helps mediate tolerance to microbes, and helps balance responses to danger signals.

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 Blueprints of Signaling Interactions between Pattern Recognition Receptors: Implications for the Design of Vaccine Adjuvants

2013 ◽  
Vol 20 (3) ◽  
pp. 427-432 ◽  
Author(s):  
Kim Timmermans ◽  
Theo S. Plantinga ◽  
Matthijs Kox ◽  
Michiel Vaneker ◽  
Gert Jan Scheffer ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Adaptive Immunity ◽  
Synergistic Effects ◽  
Interleukin 1 ◽  
Pattern Recognition Receptors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vaccine Adjuvants ◽  
Necrosis Factor Alpha ◽  
Lectin Receptors ◽  
Signaling Interactions

ABSTRACTInnate immunity activation largely depends on recognition of microorganism structures by Pattern Recognition Receptors (PRRs). PRR downstream signaling results in production of pro- and anti-inflammatory cytokines and other mediators. Moreover, PRR engagement in antigen-presenting cells initiates the activation of adaptive immunity. Recent reports suggest that for the activation of innate immune responses and initiation of adaptive immunity, synergistic effects between two or more PRRs are necessary. No systematic analysis of the interaction between the major PRR pathways were performed to date. In this study, a systematical analysis of the interactions between PRR signaling pathways was performed. PBMCs derived from 10 healthy volunteers were stimulated with either a single PRR ligand or a combination of two PRR ligands. Known ligands for the major PRR families were used: Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RigI-helicases. After 24 h of incubation, production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and IL-10 was measured in supernatants by enzyme-linked immunosorbent assay (ELISA). The consistency of the PRR interactions (both inhibitory and synergistic) between the various individuals was assessed. A number of PRR-dependent signaling interactions were found to be consistent, both between individuals and with regard to multiple cytokines. The combinations of TLR2 and NOD2, TLR5 and NOD2, TLR5 and TLR3, and TLR5 and TLR9 acted as synergistic combinations. Surprisingly, inhibitory interactions between TLR4 and TLR2, TLR4 and Dectin-1, and TLR2 and TLR9 as well as TLR3 and TLR2 were observed. These consistent signaling interactions between PRR combinations may represent promising targets for immunomodulation and vaccine adjuvant development.

The uterine cervix expresses the pattern-recognition receptors: toll-like receptors-2 and -4

2003 ◽  
Vol 189 (6) ◽  
pp. S103
Author(s):  
Yeon Mee Kim ◽  
Mi Ran Kim ◽  
Gi Jin Kim ◽  
Tinnakorn Chaiworapongsa ◽  
Ricardo Gomez ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Uterine Cervix ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptors
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