This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.
In animals, the innate immune system is the first line of defense against invading microorganisms, and the pattern-recognition receptors (PRRs) are the key components of this system, detecting microbial invasion and initiating innate immune defenses. Two families of PRRs, the intracellular NOD-like receptors (NLRs) and the transmembrane Toll-like receptors (TLRs), are of particular interest because of their roles in a number of diseases. Understanding the evolutionary history of these families and their pattern of evolutionary changes may lead to new insights into the functioning of this critical system. We found that the evolution of both NLR and TLR families included massive species-specific expansions and domain shuffling in various lineages, which resulted in the same domain architectures evolving independently within different lineages in a process that fits the definition of parallel evolution. This observation illustrates both the dynamics of the innate immune system and the effects of "combinatorially constrained" evolution, where existence of the limited numbers of functionally relevant domains constrains the choices of domain architectures for new members in the family, resulting in the emergence of independently evolved proteins with identical domain architectures, often mistaken for orthologs.
Cell-surface receptors play pivotal roles in many biological processes, including immunity, development, and reproduction, across diverse organisms. How cell-surface receptors evolve to become specialised in different biological processes remains elusive. To shed light on the immune-specificity of cell-surface receptors, we analyzed more than 200,000 genes encoding cell-surface receptors from 350 genomes and traced the evolutionary origin of immune-specific leucine-rich repeat receptor-like proteins (LRR-RLPs) in plants. Surprisingly, we discovered that the motifs crucial for co-receptor interaction in LRR-RLPs are closely related to those of the LRR-receptor-like kinase (RLK) subgroup Xb, which perceives phytohormones and primarily governs growth and development. Functional characterisation further reveals that LRR-RLPs initiate immune responses through their juxtamembrane and transmembrane regions, while LRR-RLK-Xb members regulate development through their cytosolic kinase domains. Our data suggest that the cell-surface receptors involved in immunity and development share a common origin. After diversification, their ectodomains, juxtamembrane, transmembrane, and cytosolic regions have either diversified or stabilised to recognise diverse ligands and activate differential downstream responses. Our work reveals a mechanism by which plants evolve to perceive diverse signals to activate the appropriate responses in a rapidly changing environment.
Candida albicans is a medically important pathogen, and recognition by innate immune cells is critical for its clearance. Although a number of pattern recognition receptors have been shown to be involved in recognition and phagocytosis of this fungus, the relative role of these receptors has not been formally examined. In this paper, we have investigated the contribution of the mannose receptor, Dectin-1, and complement receptor 3; and we have demonstrated that Dectin-1 is the main non-opsonic receptor involved in fungal uptake. However, both Dectin-1 and complement receptor 3 were found to accumulate at the site of uptake, while mannose receptor accumulated on C. albicans phagosomes at later stages. These results suggest a potential role for MR in phagosome sampling; and, accordingly, MR deficiency led to a reduction in TNF-alpha and MCP-1 production in response to C. albicans uptake. Our data suggest that pattern recognition receptors sample the fungal phagosome in a sequential fashion.
This study describes a method developed for predicting pattern recognition receptors (PRRs), which are an integral part of the immune system. The models developed here were trained and evaluated on the largest possible non-redundant PRRs, obtained from PRRDB 2.0, and non-pattern recognition receptors (Non-PRRs), obtained from Swiss-Prot. Firstly, a similarity-based approach using BLAST was used to predict PRRs and got limited success due to a large number of no-hits. Secondly, machine learning-based models were developed using sequence composition and achieved a maximum MCC of 0.63. In addition to this, models were developed using evolutionary information in the form of PSSM composition and achieved maximum MCC value of 0.66. Finally, we developed hybrid models that combined a similarity-based approach using BLAST and machine learning-based models. Our best model, which combined BLAST and PSSM based model, achieved a maximum MCC value of 0.82 with an AUROC value of 0.95, utilizing the potential of both similarity-based search and machine learning techniques. In order to facilitate the scientific community, we also developed a web server "PRRpred" based on the best model developed in this study (http://webs.iiitd.edu.in/raghava/prrpred/).
PRRDB 2.0 is an updated version of PRRDB that maintains comprehensive information about pattern-recognition receptors (PRRs) and their ligands. The current version of the database has ~2700 entries, which are nearly five times of the previous version. It contains extensive information about 467 unique PRRs and 827 pathogens-associated molecular patterns (PAMPs), manually extracted from ~600 research articles. It possesses information about PRRs and PAMPs that has been extracted manually from research articles and public databases. Each entry provides comprehensive details about PRRs and PAMPs that includes their name, sequence, origin, source, type, etc. We have provided internal and external links to various databases/resources (like Swiss-Prot, PubChem) to obtain further information about PRRs and their ligands. This database also provides links to ~4500 experimentally determined structures in the protein data bank of various PRRs and their complexes. In addition, 110 PRRs with unknown structures have also been predicted, which are important in order to understand the structure-function relationship between receptors and their ligands. Numerous web-based tools have been integrated into PRRDB 2.0 to facilitate users to perform different tasks like (i) extensive searching of the database; (ii) browsing or categorization of data based on receptors, ligands, source, etc. and (iii) similarity search using BLAST and Smith-Waterman algorithm.
Pattern recognition receptors (PRRs) play a crucial role in the initiation of the adaptive immune response. Immunological competence of foetal lambs occurs progressively throughout gestation, and in order to understand the role played by PRRs in foetal immunological competence, we quantified transcript expression, in the skin and spleen, of the TLRs, key C-type lectins and CARD15 during the critical second trimester. These data show that lambs express the same spectrum of PRRs as the adult but that the level of expression for most is dependent on developmental age. Key findings include: TLR1 and TLR5 are expressed at high levels in the foetus but are low in the adult; in contrast, TLR4, CD14 and CARD15 increase with age. In addition, TLR9 and TLR10 are expressed by the spleen and not the skin, while CARD15 is low in the spleen and high in the skin.
Nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are a pivotal intracellular pattern recognition receptor family. However, studies on NLR genes in important economic fish grass carp (Ctenopharyngodon idella) are sporadic. The accumulations of genomic resource and transcriptomic sequences make it feasible to conduct a systematic analysis of these genes. In this study, we systematically conducted the genome-wide study of C. idella NLR genes and characterized their phylogeny, gene structure, conserved domain, evolutionary mechanism, and expression profiles post viral or bacterial challenge. A total of 65 NLR genes were identified and clustered into five subfamilies based on structural and phylogenetic features, including eight NODs (NLR-A), five NLRP-like receptors (NLR-B), forty-seven teleost-specific NLRs (NLR-C), two members with a B30.2 domain at the C-terminal (NLR-B30.2), and three additional NLRs (other NLRs). Gene structure analysis showed that NLRs were significantly different, with exon numbers from 3 to 31. Conserved domain analysis showed that most members of C. idella NLRs had additional domains besides the typical NLR domains. Gene duplication analysis indicated that the evolution of the NLR gene family was mainly related to segment duplication. mRNA expression analysis indicated that many members were differently expressed in multiple tissues post grass carp reovirus (GCRV) or Aeromonas hydrophila infection. The expression was particularly enhanced in liver post GCRV infection, and obviously lower post A. hydrophila infection than that post GCRV infection in spleen. These results provide systematic basic data for further functional studies of NLR, and insight into the immune responses of piscine fish NLRs to pathogen infections.
cGAS (cyclic GMP-AMP synthase) is an enzyme in human cells that controls an immune response to cytosolic DNA. Upon binding DNA, cGAS synthesizes a nucleotide signal 2'3'-cGAMP that activates the protein STING and downstream immunity. Here we discover cGAS-like receptors (cGLRs) constitute a major family of pattern recognition receptors in animal innate immunity. Building on recent analysis in Drosophila , we use a bioinformatic approach to identify >3,000 cGLRs present in nearly all metazoan phyla. A forward biochemical screen of 140 animal cGLRs reveals a conserved mechanism of signaling including response to dsDNA and dsRNA ligands and synthesis of alternative nucleotide signals including isomers of cGAMP and cUMP-AMP. Using structural biology, we explain how synthesis of distinct nucleotide signals enables cells to control discrete cGLR-STING signaling pathways. Together our results reveal cGLRs as a widespread family of pattern recognition receptors and establish molecular rules that govern nucleotide signaling in animal immunity.
Pattern recognition receptors (PRRs) family plays a vital role in the initial stage of innate immune response and the subsequent activation of adaptive immunity. Increasing evidences have indicated that several PRRs play critical roles in the progress of inflammation and tumorigenesis. However, the comprehensive significance of PRRs family in clinical prognosis of different cancers is still elusive.
Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition receptors (PRRs) on susceptibility to RVVC.
Mast cells (MCs) are involved in several immune-related responses, including those in bacterial infections, autoimmune diseases, inflammatory bowel diseases, and cancer, among others. MCs identify microorganisms by pattern recognition receptors (PRRs), activating a secretory response. Interleukin (IL)-10 has been described as an important modulator of MC responses; however, its role in PRR-mediated activation of MC is not fully understood. We analyzed the activation of TLR2, TLR4, TLR7 and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mucosal-like MCs (MLMCs) and peritoneum-derived cultured MCs (PCMCs) from IL-10-/- and wild-type (WT) mice. IL-10-/- mice showed a reduced expression of TLR4 and NOD2 at week 6 and TLR7 at week 20 in MLMC. In MLMC and PCMC, TLR2 activation induced a reduced secretion of IL-6 and TNFα in IL-10-/- MCs. TLR4- and TLR7-mediated secretion of IL-6 and TNFα was not detected in PCMCs. Finally, no cytokine release was induced by NOD2 ligand, and responses to TLR2 and TLR4 were lower in MCs at 20 weeks. These findings indicate that PRR activation in MCs depends on the phenotype, ligand, age, and IL-10.
Pattern recognition receptors (PRRs) are essential in recognizing specific pathogen-associated molecular patterns (PAMPs) on microbes and triggering responses to eliminate the invading pathogens. Previous genomic studies have revealed a great number of PRR genes in the Pacific oyster Crassostrea gigas, a sessile and filter-feeder marine bivalve belonging to the phylum Mollusca. On the survey of PRRs in the assembly oyster reference genome version 9, a total of 1084 PRRs were identified, which were composed of at least 12 gene families. Some of the gene families were significantly expanded, including C-type lectins (CTLs), fibrinogen-related proteins (FREPs), scavenger receptor cysteine-rich repeat protein (SRCRs), leucine-rich repeat (LRR)-only proteins (LRRops), and especially C1q domain-containing proteins (C1qDCs). The transcriptomic profiles of these abundant PRRs in response to PAMP treatments were investigated by RNA-Seq using the SOLiD EZ BeadTM system. Compared to the control library, there were 6,655, 7,273, 7,593, 6,830, 6687 and 8250 differentially expressed genes in the haemocytes of oysters in response to lipopolysaccharide (LPS) stimulation for 6 h, 12 h and 24 h, and peptidoglycan (PGN), glucan (GLU) and poly I:C (IC) stimulation for 12 h, respectively. After stimulation for 12 h, there were 134, 97, 114 and 159 genes up-regulated in the LPS, PGN, GLU and IC library, respectively. Most of the gene families involved in immune response towards PAMPs were C1qDCs, CTLs and FREPs, while only a few members of LRR and immunoglobin-containing proteins (LRRIGs), retinoic acid-inducible gene I [RIG-I]-like receptors (RLRs) and Toll like receptors (TLRs) were up-regulated. After LPS stimulation, the expression level of 258 non-redundant PRR genes in oyster haemocytes increased significantly with different expression pattern, and most of them were C1qDCs, CTLs, LRRops and FREPs. The transcriptomic analyses indicated that there was a dynamic and orchestrated specific expression regulation of numerous PRR genes in response to pathogen invasion. The expanded PRR gene family members were differentiated with more specific functional responses to certain PAMPs rather than the versatile ones. Based on the different expression pattern during the LPS stimulation, the oyster PRRs could be assigned into three consecutive steps in the response against pathogen invading. All the results would provide useful information for future studies of oyster PRRs and deep insight into the researches on invertebrate innate immunity.
An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.
Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), are censoring receptors for molecules derived from bacteria, viruses, and fungi. The PRR system is a prerequisite for proper responses to pathogens, for example by cytokine production, resulting in pathogen eradication. Many cases of polymorphisms in PRR genes affecting the immune response and disease susceptibility are known in humans and mice.
Endometriosis is characterized by repeated inflammatory changes and serious adhesions, inducing innate and adaptive immune responses within the abdominal cavity. To assess these immune responses, we evaluated the levels of expression of Toll-like receptors (TLR)-1, -2, -4, -5, and -9; nucleotide-binding oligomerization domains (NOD)-1 and -2; interleukins-1β, -6, -8, -10, and -12; interferon-γ; tumor necrosis factor-α; inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS); and immunoglobulins (Igs) in patients with endometriosis.
The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2.
RIG-I and MDA5 sense virus-derived short 5'ppp blunt-ended or long dsRNA, respectively, causing interferon production. Non-signaling LGP2 appears to positively and negatively regulate MDA5 and RIG-I signaling, respectively. Co-crystal structures of chicken (ch) LGP2 with dsRNA display a fully or semi-closed conformation depending on the presence or absence of nucleotide. LGP2 caps blunt, 3' or 5' overhang dsRNA ends with 1 bp longer overall footprint than RIG-I. Structures of 1:1 and 2:1 complexes of chMDA5 with short dsRNA reveal head-to-head packing rather than the polar head-to-tail orientation described for long filaments. chLGP2 and chMDA5 make filaments with a similar axial repeat, although less co-operatively for chLGP2. Overall, LGP2 resembles a chimera combining a MDA5-like helicase domain and RIG-I like CTD supporting both stem and end binding. Functionally, RNA binding is required for LGP2-mediated enhancement of MDA5 activation. We propose that LGP2 end-binding may promote nucleation of MDA5 oligomerization on dsRNA.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: