scholarly journals Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Guo-Yun Chen ◽  
Nicholas K Brown ◽  
Wei Wu ◽  
Zahra Khedri ◽  
Hai Yu ◽  
...  

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced disruption of TLR4:Siglec E/F interactions. Absence of Neu1 in hematopoietic cells or systematic treatment with sialidase inhibitor Neu5Gc2en protected mice against endotoxemia. Our data raised an intriguing possibility of a broad repression of TLR function by Siglecs and a sialidase-mediated de-repression that allows positive feedback of TLR activation during infection.

2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Matevž Rumpret ◽  
Helen J. von Richthofen ◽  
Victor Peperzak ◽  
Linde Meyaard

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.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1123
Author(s):  
Helena Choltus ◽  
Marilyne Lavergne ◽  
Coraline De Sousa Do Outeiro ◽  
Karen Coste ◽  
Corinne Belville ◽  
...  

Preterm prelabor ruptures of fetal membranes (pPROM) are a pregnancy complication responsible for 30% of all preterm births. This pathology currently appears more as a consequence of early and uncontrolled process runaway activation, which is usually implicated in the physiologic rupture at term: inflammation. This phenomenon can be septic but also sterile. In this latter case, the inflammation depends on some specific molecules called “alarmins” or “damage-associated molecular patterns” (DAMPs) that are recognized by pattern recognition receptors (PRRs), leading to a microbial-free inflammatory response. Recent data clarify how this activation works and which receptor translates this inflammatory signaling into fetal membranes (FM) to manage a successful rupture after 37 weeks of gestation. In this context, this review focused on two PRRs: the receptor for advanced glycation end-products (RAGE) and the NLRP7 inflammasome.


Author(s):  
Lin Cui ◽  
Xiuqing Wang ◽  
Dekai Zhang

Gastric cancer (GC) is one of the most common cancers in the world, and the incidence of gastric cancer in Asia appears to increase in recent years. Although there is a lot of improvement in treatment approaches, the prognosis of GC is poor. So it is urgent to search for a novel and more effective treatment to improve the survival rate of patients. Both innate immunity and adaptive immunity are important in cancer. In the innate immune system, pattern recognition receptors (PRRs) activate immune responses by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs). Many studies have reported that TLRs are involved in the occurrence, development, and treatment of GC. Therefore, TLRs are potential targets for immunotherapy to gastric cancer. However, gastric cancer is a heterogeneous disorder, and TLRs function in GC is complex. TLRs agonists can be potentially used not only as therapeutic agents to treat gastric cancer but also as adjuvants in conjunction with other immunotherapies. They might provide a promising new target for GC treatment. In the review, we sort out the mechanism of TLRs involved in tumor immunity and summarize the current progress in TLRs-based therapeutic approaches and other immunotherapies in the treatment of GC.


2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Clare Bryant ◽  
Tom P. Monie

Pattern Recognition Receptors (PRRs, [104]) (nomenclature as agreed by NC-IUPHAR sub-committee on Pattern Recognition Receptors, [18]) participate in the innate immune response to microbial agents, the stimulation of which leads to activation of intracellular enzymes and regulation of gene transcription. PRRs express multiple leucine-rich regions to bind a range of microbially-derived ligands, termed PAMPs or pathogen-associated molecular patterns or endogenous ligands, termed DAMPS or damage-associated molecular patterns. These include peptides, carbohydrates, peptidoglycans, lipoproteins, lipopolysaccharides, and nucleic acids. PRRs include both cell-surface and intracellular proteins. PRRs may be divided into signalling-associated members, identified here, and endocytic members, the function of which appears to be to recognise particular microbial motifs for subsequent cell attachment, internalisation and destruction. Some are involved in inflammasome formation, and modulation of IL-1β cleavage and secretion, and others in the initiation of the type I interferon response. PRRs included in the Guide To PHARMACOLOGY are:Catalytic PRRs (see links below this overview)Toll-like receptors (TLRs)Nucleotide-binding oligomerization domain, leucine-rich repeat containing receptors (NLRs, also known as NOD (Nucleotide oligomerisation domain)-like receptors)RIG-I-like receptors (RLRs)Caspase 4 and caspase 5 Non-catalytic PRRsAbsent in melanoma (AIM)-like receptors (ALRs)C-type lectin-like receptors (CLRs)Other pattern recognition receptorsAdvanced glycosylation end-product specific receptor (RAGE)


2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Clare Bryant ◽  
Tom P. Monie

Pattern Recognition Receptors (PRRs, [83]) (nomenclature as agreed by NC-IUPHAR sub-committee on Pattern Recognition Receptors, [15]) participate in the innate immune response to microbial agents, the stimulation of which leads to activation of intracellular enzymes and regulation of gene transcription. PRRs express multiple leucine-rich regions to bind a range of microbially-derived ligands, termed PAMPs or pathogen-associated molecular patterns or endogenous ligands, termed DAMPS or damage-associated molecular patterns. These include peptides, carbohydrates, peptidoglycans, lipoproteins, lipopolysaccharides, and nucleic acids. PRRs include both cell-surface and intracellular proteins. PRRs may be divided into signalling-associated members, identified here, and endocytic members, the function of which appears to be to recognise particular microbial motifs for subsequent cell attachment, internalisation and destruction. Some are involved in inflammasome formation, and modulation of IL-1β cleavage and secretion, and others in the initiation of the type I interferon response. PRRs included in the Guide To PHARMACOLOGY are:Catalytic PRRs (see links below this overview)Toll-like receptors (TLRs)Nucleotide-binding oligomerization domain, leucine-rich repeat containing receptors (NLRs, also known as NOD (Nucleotide oligomerisation domain)-like receptors)RIG-I-like receptors (RLRs)Caspase 4 and caspase 5 Non-catalytic PRRsAbsent in melanoma (AIM)-like receptors (ALRs)C-type lectin-like receptors (CLRs)Other pattern recognition receptorsAdvanced glycosylation end-product specific receptor (RAGE)


Author(s):  
О.Ю. Филатов ◽  
В.А. Назаров

Данная статья обобщает накопившуюся на сегодняшний день информацию о многообразии образраспознающих рецепторов, их роли в регуляции иммунной системы. Распознавание патогена врожденным иммунитетом происходит с помощью рецепторов к широкому спектру антигенов за счет выделения нескольких высоко консервативных структур микроорганизмов. Эти структуры были названы патоген-ассоциированные образы (Patogen-Associated Molecular Patterns - PAMP). Наиболее изученными являются липополисахарид грамм отрицательных бактерий (LPS), липотейхоевые кислоты, пептидогликан (PGN), CpG мотивы ДНК и РНК. Рецепторы, распознающие PAMP, называются PRR. Данная группа рецепторов также распознает молекулы, образующиеся при повреждении собственных тканей. Такие молекулярные структуры называются Damage-Associated Molecular Patterns (DAMP), или образы, ассоциированные с повреждением. В качестве DAMP могут выступать белки теплового шока, хроматин, фрагменты ДНК. В зависимости от локализации, образраспознающие рецепторы принято разделять на: расположенные на мембране Toll-подобные рецепторы (Toll-like receptors, TLR) и рецепторы лектина С-типа (C-type lectin receptors, CLR), а также расположенные в цитоплазме NOD-подобные рецепторы (NOD-like receptors, NLR) и цитоплазматические РНК- и ДНК-сенсоры. Сегодня у человека известно 10 типов TLR, часть из которых расположена на поверхности (TLR1-TLR6, TLR10) большинства клеток, в том числе макрофагов, В-лимфоцитов и дендритных клеток, а часть - в эндосомах (TLR3, TLR7-TLR9). CLR представляет из себя семейство рецепторов, расположенных на мембране и имеющих домены распознавания углеводов (CRD), или структурно сходные лектиноподобные домены типа C (CTLD). В данном семействе рецепторов принято по происхождению и структуре выделять 17 групп. CLR активно участвуют в противогрибковой иммунной защите, а также они играют роль в защите и от других типов микроорганизмов. NOD (нуклеотидсвязывающий и олигомеризационный домен)-подобные рецепторы расположены в цитоплазме. Благодаря этим рецепторам, патоген, который избежал распознавания на поверхности мембраны, сталкивается со вторым уровнем распознавания уже внутри клетки. В данной статье рассматриваются пути активации образраспознающих рецепторов, их эффекты и применение данных эффектов в медицине. This article summarizes currently available information about the variety of image-recognizing receptors and their role in regulation of the immune system. Pathogen recognition by the innate immunity is mediated by receptors to a wide range of antigens via recognition of several highly conservative structures of microorganisms. These structures were named pathogen-associated images or PAMP (pathogen-associated molecular pattern). The best studied types of such structures include lipopolysaccharide (LPS) of gram-negative bacteria, lipoteichoic acids, peptidoglycan (PGN), and CpG DNA and RNA motifs. PAMP-recognizing receptors (PRRS) are a group of receptors, which also recognize molecules released during damage of host tissues. Such molecular structures are called DAMPS (damage-associated molecular patterns) or damage-associated images. Heat shock proteins, chromatin, and DNA fragments may act as DAMPS. Depending on the localization, image-recognizing receptors are generally classified as membrane-located Toll-like receptors (TLR) and C-type lectin receptors (CLR), as well as cytoplasmic NOD-like receptors (NLR) and cytoplasmic RNA and DNA sensors. Today, 10 types of human TLR are known. Some of them are located on the surface (TLR1-TLR6, TLR10) of most cells, including macrophages, B-cells, and dendritic cells, and some are present in endosomes (TLR3, TLR7-TLR9). CLR is a family of membrane receptors that have carbohydrate recognition domains (CRD) or structurally similar lectin-like type C domains (CTLD). Seventeen groups are distinguished within this receptor family based on their origin and structure. CLRs are actively involved in antifungal immune defense and also play a role in protection against other types of microorganisms. NOD (nucleotide-binding and oligomerization domain)-like receptors are present in the cytoplasm. These receptors provide the second level of recognition inside the cell for the pathogens that have escaped recognition on the membrane surface. This article discusses activation pathways of image-recognizing receptors, their effects, and the use of such effects in medicine.


2011 ◽  
Vol 108 (2) ◽  
pp. 235-248 ◽  
Author(s):  
Yury I. Miller ◽  
Soo-Ho Choi ◽  
Philipp Wiesner ◽  
Longhou Fang ◽  
Richard Harkewicz ◽  
...  

Author(s):  
Jane Kwok ◽  
Kenrie P. Y. Hui ◽  
Julien Lescar ◽  
Masayo Kotaka

The human innate immune system can detect invasion by microbial pathogens through pattern-recognition receptors that recognize structurally conserved pathogen-associated molecular patterns. Retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) are one of the two major families of pattern-recognition receptors that can detect viral RNA. RIG-I, belonging to the RLH family, is capable of recognizing intracellular viral RNA from RNA viruses, including influenza virus and Ebola virus. Here, full-length human RIG-I (hRIG-I) was cloned inEscherichia coliand expressed in a recombinant form with a His-SUMO tag. The protein was purified and crystallized at 291 K using the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 2.85 Å resolution; the crystal belonged to space groupF23, with unit-cell parametersa = b=c= 216.43 Å, α = β = γ = 90°.


Author(s):  
Yusuke Saijo ◽  
Eliza Loo ◽  
Yuri Tajima ◽  
Kohji Yamada ◽  
Shota Kido ◽  
...  

In plants, a first layer of inducible immunity is conferred by pattern recognition receptors (PRRs) that bind microbe- and damage-associated molecular patterns (MAMPs/DAMPs, respectively) to activate pattern-triggered immunity (PTI). PTI is strengthened or followed by another potent form of immunity when intracellular receptors recognize pathogen effectors, termed effector-triggered immunity (ETI). Immunity signaling regulators have been reported to influence abiotic stress responses as well, yet the governing principles and mechanisms remain ambiguous. Here, we report that PRRs of a leucine-rich repeat ectodomain also confer salt tolerance in Arabidopsis thaliana, following recognition of cognate ligands, such as bacterial flagellin (flg22 epitope) and EF-Tu (elf18 epitope), and the endogenous Pep peptides. Pattern-triggered salt tolerance (PTST) requires authentic PTI signaling components, namely the PRR-associated kinases BAK1 and BIK1, and the NADPH oxidase RBOHD. Exposure to salt stress induces the release of Pep precursors, pointing to the involvement of the endogenous immunogenic peptides in developing plant tolerance to high salinity. Transcriptome profiling reveals an inventory of PTST target genes, which increase or acquire salt responsiveness following a pre-exposure to immunogenic patterns. In good accordance, plants challenged with non-pathogenic bacteria also acquired salt tolerance in a manner dependent on PRRs. Our findings provide insight into signaling plasticity underlying biotic-abiotic stress cross-tolerance in plants conferred by PRRs.


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