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Results for “Receptors, Pattern Recognition”

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At least 127 records · Page 7Linked to original sources

PubMed2006

DC-SIGN and immunoregulation.

Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.

Cell Adhesion Molecules↗

PubMed2006

Intestinal epithelial cell signalling and host-derived negative regulators under chronic inflammation: to be or not to be activated determines the balance towards commensal bacteria.

Advancing knowledge regarding the cellular mechanisms of intestinal inflammation has led to a better understanding of the disease pathology in patients with chronic disorders of the gut including inflammatory bowel disease, coeliac disease, lymphocytic colitis and irritable bowel syndrome. An emerging new paradigm suggests that changes in the homeostasis of bacteria- and host-derived signal transduction at the epithelial cell level may lead to functional and immune disturbances of the intestinal epithelium. It has become clear from numerous studies that enteric bacteria are a critical component in the development and prevention/treatment of chronic intestinal inflammation. Signal-specific activation of mitogen-activated protein kinases (MAPK), interferon-regulated factors (IRF) and the transcription factor NF-kappaB through pattern recognition receptor signalling effectively induce inflammatory defence mechanisms. Unbalanced activation of these innate signalling pathways because of host genetic predispositions and/or the lack of adequate anti-inflammatory feedback mechanisms may turn a physiological response into a pathological situation including failure of bacterial clearance and development of chronic inflammation. Host-derived regulators from the immune and enteric nerve system crosstalk to the innate signalling network of the intestinal epithelium in order to shape the extent and duration of inflammatory processes.

Animals↗

PubMed2002

[Recent advances in innate immune host defense--hose defense lectins and endotoxin receptors].

Accumulating evidence has revealed that CD14 and Toll-like receptors (TLRs) function as pattern recognition receptors for broad ranges of pathogens. The structural characteristics of these proteins is that they possess leucine-rich repeats, which appear to be involved in protein-protein interaction. We have shown that the extracellular TLR2 domain directly binds to peptidoglycan (PGN) which is abundant in the cell wall of Gram-positive bacteria and that the N-terminal region of TLR2 is critical for the recognition of PGN. Surfactant proteins A and D (pulmonary collectins) function as host defense lectins and play important roles in innate immunity in the lung-Collectins including SP-A, SP-D and mannose-binding proteins can bind CD14. We have demonstrated that SP-A modulates the cellular response to smooth and rough lipopolysaccharides (LPS) by interaction with CD14. In addition, this protein has been revealed to function as a negative regulator against PGN-induced TNF-alpha secretion from macrophages through direct interaction with TLR2. We propose that SP-A modulates inflammatory responses against the bacterial components by interaction with pattern-recognition receptors.

Animals↗

PubMed2025

Repeats mimic pathogen-associated patterns across a vast evolutionary landscape.

An emerging hallmark of many human diseases is transcription of typically silenced repetitive DNA containing pathogen-associated molecular patterns (PAMPs). These PAMPs engage the innate immune system via pattern recognition receptors (PRRs)-a phenomenon known as viral mimicry. We propose a statistical physics framework to quantify viral mimicry by measuring "selective forces" that enrich PAMPs compared to a genome-wide reference distribution. We validate our predictions by identifying repeats that bind different PRRs and show potential viral mimics in different repeat families across eukaryotic genomes, suggesting shared mechanisms drive emergence and retention. We propose two non-exclusive evolutionary hypotheses. The first "repeat-centric" hypothesis posits PAMPs are integral to the repeat life cycle and are therefore enriched as they mediate repeat expansion. The second "organism-centric" hypothesis proposes viral mimicry functions as a cell-intrinsic feedback mechanism for sensing and reacting to transcriptional dysregulation, which provides a selective pressure to maintain PAMPs in genomes.

Humans↗

PubMed2006

Beta 1, 3-glucan recognition protein from the mosquito, Armigeres subalbatus, is involved in the recognition of distinct types of bacteria in innate immune responses.

The activation of an immune response to invading microorganisms generally requires recognition by pattern recognition receptors. Beta 1, 3-glucan recognition proteins (GRPs) have specific affinity for beta 1, 3-glucan, a component on the surface of fungi and bacteria. In this study, we show that GRP from Armigeres subalbatus mosquitoes (AsGRP) is able to bind different bacterial species, and that this binding varies from species to species and is independent of Gram type. AsGRP knockdown with double-stranded RNA increases the mortality of mosquitoes to those bacteria that strongly bind AsGRP, but not to bacteria that do not detectably bind AsGRP. This increase in susceptibility is partially evidenced by decreased melanization in Salmonella typhimurium. Furthermore, AsGRP expression is differentially affected by the presence of different species of bacteria. These results demonstrate that AsGRP is selective in its affinity to different bacteria and; therefore, plays a role in the antibacterial immune response of mosquitoes.

Animals↗

PubMedDate not supplied

CpG motifs to modulate innate and adaptive immune responses.

The vertebrate adaptive and innate immune systems have evolved to protect the host from pathogen infections. To achieve this mission, the innate immune system developed particular receptors, termed "pattern recognition receptors" (PRRs). These PRRs selectively bind certain types of structures expressed by pathogens but in principal absent in vertebrates. One of the best understood receptors is the Toll-like receptor (TLR) 9 that recognizes CpG sequence motifs in bacterial and viral DNA. Different classes of short synthetic phosphorothioate-stabilized CpG oligodeoxynucleotides were developed and are currently in human clinical trials in the fields of infectious disease, cancer, and asthma/allergy.

Animals↗

PubMed2004

Pneumocystis activates human alveolar macrophage NF-kappaB signaling through mannose receptors.

Alveolar macrophages (AM) represent important effector cells in the innate immune response to the AIDS-related pathogen Pneumocystis, but the early AM host defense signaling events are poorly defined. Using AM from healthy individuals, we showed in the present study that Pneumocystis organisms stimulate AM NF-kappaB p50 and p65 nuclear translocation in a time-dependent and multiplicity-of-infection-dependent manner as determined by electrophoretic mobility shift assay and immunofluorescence microscopy and that NF-kappaB nuclear translocation is associated with I-kappaB phosphorylation. Importantly, competitive inhibition of mannose receptor and targeted short interfering RNA-mediated gene suppression of mannose receptor mRNA and protein is associated with complete elimination of NF-kappaB nuclear translocation in response to Pneumocystis. Furthermore, human immunodeficiency virus (HIV) infection of AM (as a model human disease state of reduced AM mannose receptor expression and function) inhibits Pneumocystis-mediated NF-kappaB nuclear translocation and is associated with reduced I-kappaB phosphorylation and reduced interleukin-8 (IL-8) release. In contrast, NF-kappaB nuclear translocation and IL-8 release in response to lipopolysaccharide are intact in AM from both healthy and HIV-infected individuals, indicating that the observed impairment is not a global disturbance of the NF-kappaB pathway. Thus, in addition to phagocytic and endocytic effector functions, the present study identifies mannose receptors as pattern recognition receptors capable of NF-kappaB activation in response to infectious non-self challenge. AM mannose receptor-mediated NF-kappaB activation may represent an important mechanism of the host cell response to Pneumocystis, and altered NF-kappaB activation in the context of HIV infection may impair a critical innate immune signaling response and may contribute to pathogenesis of opportunistic lung infections.

Adult↗

PubMed2004

Thematic review series: the immune system and atherogenesis. Recent insights into the biology of macrophage scavenger receptors.

Scavenger receptors were originally defined by their ability to bind and internalize modified lipoproteins. Macrophages express at least six structurally different cell surface receptors for modified forms of LDL that contribute to foam cell formation in atherosclerosis. In addition to their role in the pathology of atherosclerosis, macrophage scavenger receptors, especially SR-A, play critical roles in innate immunity, apoptotic cell clearance, and tissue homeostasis. In this review, we highlight recent advances in understanding the biology of macrophage scavenger receptors as pattern recognition receptors for both infectious nonself (pathogens) and modified self (apoptotic cells and modified LDL). We critically evaluate the potential of scavenger receptors and their ligands as targets for therapeutic intervention in human disease.

Animals↗

PubMedDate not supplied

Implication of innate immunity in the pathogenesis of biliary atresia.

Biliary atresia (BA) is a complex disorder for which the etiology is still far from clear. Newborn infants that develop BA may carry certain genetic defects, resulting in susceptibility to uncertain pathogens with characteristic pathogen-associated molecular patterns (PAMPs). The pathogens with their characteristic PAMPs in turn lead to activation of the innate immune system by triggering pattern recognition receptors on the immune cells. Toll-like receptors (TLRs) are the most recognized pattern recognition receptors and TLR signaling is the telltale sign of activation of innate immunity. The activation of TLR and the innate immune system in BA is demonstrated by the up-regulation of TLR7 and by the association of promoter polymorphism of CD14 with BA. The antimicrobial peptide hepcidin and MxA, a protein downstream of TLR7 signaling, which is also known as a highly specific marker for type I IFN signaling, are also found highly expressed in the early stage of BA. This review examines the known components of innate immunity involved in BA and outlines the potential role of the innate immune system, in cooperation with adaptive immunity, in the pathogenesis of BA.

Animals↗

PubMed2006

Toll-like receptor function and signaling.

Mammals sense pathogen invasion through pattern-recognition receptors. A group of transmembrane proteins, Toll-like receptors (TLRs), play critical roles as pattern-recognition receptors. They are mainly expressed on antigen-presenting cells, such as macrophages or dendritic cells, and their signaling activates antigen-presenting cells to provoke innate immunity and to establish adaptive immunity. Each TLR has common effects, such as inflammatory cytokine induction or upregulation of costimulatory molecule expression, but also has its specific function, exemplified by type I IFN-inducing ability. These immunoadjuvant effects are not only critical in antimicrobial immunity but are also involved in manifestations of autoimmunity. Furthermore, some TLR agonists are now promising therapeutic tools for various immune disorders, including allergy. Therefore understanding molecular mechanisms on TLRs should be quite useful in the development of therapeutic maneuvers against allergy and autoimmune diseases.

Animals↗

PubMed2006

Innate immune recognition of viral infection.

Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type I interferon and inflammatory cytokines and leads to dendritic cell maturation and establishment of antiviral immunity. Cells also express cytoplasmic RNA helicases that function as alternative pattern-recognition receptors through recognition of double-stranded RNA produced during virus replication. These two classes of pattern-recognition receptor molecules are expressed in different intracellular compartments and induce type I interferon responses via distinct signaling pathways.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Lateral diffusion of Toll-like receptors reveals that they are transiently confined within lipid rafts on the plasma membrane.

The innate immune system utilises pattern recognition receptors in order to recognise microbial conserved molecular patterns. The family of Toll-like receptors (TLRs) has been shown to act as the main pattern recognition receptors for the innate immune system. Using biochemical as well as fluorescence imaging techniques, TLR2 and TLR4 were found to be recruited within microdomains upon stimulation by bacterial products. Furthermore their lateral diffusion in the cell membrane as determined by fluorescence recovery after photobleaching revealed that upon stimulation by bacterial products TLRs encounter barriers to their lateral movement, thus supporting the notion that specialised domains on the plasma membrane facilitate the innate recognition.

Animals↗

PubMed2006

C-type lectins on dendritic cells and their interaction with pathogen-derived and endogenous glycoconjugates.

Human C-type lectin receptors (CLRs) characteristically bind glycosylated ligands in a Ca(2+)-dependent way via their carbohydrate recognition domain (CRD). Their carbohydrate preference is dependent on the amino acid sequence in the CRD domain and on the ability and flexibility of the CRD domain to accommodate sugar moieties that are located at different distances from each other in the glycoconjugate. Although microbial and vertebrate cells are able to produce similar polysaccharide chains, the density of carbohydrates on microbes is much higher compared to vertebrate cells. Despite this difference, carbohydrates present on both cell types can be recognized by the CLRs. These receptors are predominantly expressed by antigen presenting cells such as dendritic cells. In addition to the Toll-like receptor family, CLRs function as pattern recognition receptors by recognizing glycosylated patterns on pathogens. This usually results in internalization of the pathogen, lysosomal degradation and subsequent loading of pathogen-derived peptides into major histocompatibility complex molecules for antigen presentation. However, several pathogens have developed ways to exploit the CLRs to evade immune eradication by for example escaping from the lysosomal degradation pathway or by inducing anti-inflammatory cytokines. When CLRs bind endogenous glycosylated ligands they mediate several processes like cell-cell adhesion and clearance of aberrant cells like tumor cells or apoptotic cells.

Amino Acid Sequence↗

PubMed2006

Dependence on p38 MAPK signalling in the up-regulation of TLR2, TLR4 and TLR9 gene expression in Trichomonas vaginalis-treated HeLa cells.

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that recognize conserved pathogen-associated molecular patterns (PAMPs) synthesized by micro-organisms. Despite the essential requirement for TLRs in prokaryotic infection, the pattern and regulation of TLR gene expression by Trichomonas vaginalis in the mucocutaneous barrier are still unknown. Our hypothesis is that T. vaginalis-infected epithelial cells are major effector cells in the skin barrier. These cells function as a central regulator of TLR gene expression, thus accelerating the process of barrier dysfunction via increased release of chemokines and proinflammatory cytokines. To test this hypothesis, RT-PCR was performed on TLRs, interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha. Stimulation of HeLa cells by T. vaginalis was observed to up-regulate TLR2, 4 and 9 mRNA expression as well as that of IL-8 and TNF-alpha. To further clarify the molecular mechanism of barrier devastation triggered by these up-regulatory stimuli, we examined the profiles of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB activation in HeLa cells using specific inhibitors. Interestingly, pretreatment of HeLa cells with the p38 MAPK inhibitor SB203580 demonstrated inhibition of T. vaginalis-induced up-regulation of TLR2, 4, and 9 mRNA expression. By contrast, inhibition of ERK or NF-kappaB activation failed to block T. vaginalis-induced up-regulation of TLR9 mRNA expression or TLR2 and TLR4 mRNA expression, respectively. In addition, pretreatment with SB203580 reduced epithelium-derived IL-8 and TNF-alpha release evoked by T. vaginalis. Our results show that T. vaginalis infection of the mucocutaneous barrier could up-regulate TLR2, 4 and 9 gene expression via the p38 MAPK signalling pathway in epithelial cells; this process then leads to modulation of p38 MAPK-dependent IL-8 and TNF-alpha release from the epithelium.

Animals↗

PubMed2006

Recognition of pathogenic microorganisms by Toll-like receptors.

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns (PAMPs) by TLRs, either alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of innate immune response. Recent studies have demonstrated a crucial involvement of TLRs in the recognition of all the major classes of microbial pathogens. By studying fungal infection in knock-out mice deficient in either TLRs or TLR-associated adaptor molecules, it appeared that specific TLRs play differential roles in the activation of the various arms of the innate immune response. Recent data also suggest that TLRs offer escape mechanisms to certain pathogenic microorganisms, especially through TLR2-driven induction of antiinflammatory cytokines. These new data have substantially increased our knowledge of the recognition of microbial pathogens, and this remains one of the most active areas of research in the field of infectious diseases.

Animals↗

PubMed2003

Modulation of Toll-like Receptor 9 Responses through Synthetic Immunostimulatory Motifs of DNA.

Bacterial, plasmid, and synthetic DNA containing unmethylated CpG dinucleotides in specific sequence contexts activate the vertebrate innate immune system. A pattern recognition receptor (PRR), toll-like receptor 9 (TLR9), recognizes CpG DNA and activates signaling cascade leading to the secretion of a number of cytokines and chemokines. Our extensive structure-immunostimulatory activity relationship studies showed that a number of synthetic pyrimidine (Y) and purine (R) nucleotides are accepted by the receptor as substitutes for natural deoxycytidine and deoxyguanosine in a CpG dinucleotide. These studies permitted development of synthetic immunostimulatory motifs YpG, CpR, and YpR and established the nucleotide motif recognition pattern of the receptor. A number of site-specific chemical modifications in the flanking sequences to the CpG dinucleotide permitted modulation of immunostimulatory affects in a predictable manner. Our studies also showed that TLR9 recognizes and reads the CpG DNA sequence from the 5'-end. Design of oligonucleotides with two 5'-ends, immunomers, resulted in potent immunomodulatory agents with distinct cytokine profiles. Immunomers containing synthetic immunostimulatory motifs produced different cytokine induction profiles compared with natural CpG motifs. Importantly, some of these synthetic motifs showed optimal activity in both mouse and human systems without requiring to change sequences, suggesting overriding the species-dependent specificity of the receptor by the use of synthetic motifs. In this article, we review current understanding of structural recognition and functional modulation of TLR9 receptor by second-generation immunomodulatory oligonucleotides and their potential application as wide spectrum therapeutic agents.

3' Flanking Region↗

PubMed2005

Varicella-zoster virus activates inflammatory cytokines in human monocytes and macrophages via Toll-like receptor 2.

The pattern recognition receptor Toll-like receptor 2 (TLR2) has been implicated in the response to several human viruses, including herpes simplex viruses (types 1 and 2) and cytomegalovirus. We demonstrated that varicella-zoster virus (VZV) activates inflammatory cytokine responses via TLR2. VZV specifically induced interleukin-6 (IL-6) in human monocytes via TLR2-dependent activation of NF-kappaB, and small interfering RNA designed to suppress TLR2 mRNA reduced the IL-6 response to VZV in human monocyte-derived macrophages. Unlike other herpesviruses, the cytokine response to VZV was species specific. VZV did not induce cytokines in murine embryonic fibroblasts or in a mouse cell line, although VZV did activate NF-kappaB in a human cell line expressing a murine TLR2 construct. Together, these results suggest that TLR2 may play a role in the inflammatory response to VZV infection.

Animals↗

PubMed2001

Toll-like receptors: critical proteins linking innate and acquired immunity.

Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.

Animals↗