Pathophysiological Implication of Pattern Recognition Receptors in Fetal Membranes Rupture: RAGE and NLRP Inflammasome

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.

Download Full-text

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

eLife ◽

10.7554/elife.04066 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 66

Author(s):

Guo-Yun Chen ◽

Nicholas K Brown ◽

Wei Wu ◽

Zahra Khedri ◽

Hai Yu ◽

...

Keyword(s):

Pattern Recognition ◽

Direct Interaction ◽

Pattern Recognition Receptors ◽

Immunoglobulin Superfamily ◽

Lectin Receptors ◽

Sialidase Inhibitor ◽

Tlr4 Ligand ◽

Tlr4 Activation ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

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.

Download Full-text

On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

Mediators of Inflammation ◽

10.1155/2014/251451 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Rafał Rzepka ◽

Barbara Dołęgowska ◽

Aleksandra Rajewska ◽

Sebastian Kwiatkowski

Keyword(s):

Acute Inflammation ◽

Preterm Labour ◽

Premature Labour ◽

Advanced Glycation ◽

Chronic Inflammatory Response ◽

Glycation End Products ◽

End Products ◽

Stromal Cell Derived Factor ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs), receptors for advanced glycation end products (RAGE), negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1) and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

Download Full-text

Inhibitory pattern recognition receptors

Journal of Experimental Medicine ◽

10.1084/jem.20211463 ◽

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.

Download Full-text

Mammalian Cytosolic Galectins Act as Damage-Associated Molecular Patterns, Resolution-Associated Molecular Patterns, and Pattern-Recognition Receptors in Innate Immunity

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering ◽

10.1016/b978-0-12-819475-1.00052-3 ◽

2020 ◽

Author(s):

Sachiko Sato

Keyword(s):

Pattern Recognition ◽

Innate Immunity ◽

Pattern Recognition Receptors ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Download Full-text

Journey to a Receptor for Advanced Glycation End Products Connection in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315527 ◽

2020 ◽

Author(s):

Divya Roy ◽

Ravichandran Ramasamy ◽

Ann Marie Schmidt

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Advanced Glycation End Products ◽

Tissue Damage ◽

Advanced Glycation ◽

Molecular Pattern ◽

Increased Risk ◽

Glycation End Products ◽

End Products ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide and the pandemic has yet to wane. Despite its associated significant morbidity and mortality, there are no definitive cures and no fully preventative measures to combat SARS-CoV-2. Hence, the urgency to identify the pathobiological mechanisms underlying increased risk for and the severity of SARS-CoV-2 infection is mounting. One contributing factor, the accumulation of damage-associated molecular pattern molecules, is a leading trigger for the activation of nuclear factor-kB and the IRF (interferon regulatory factors), such as IRF7. Activation of these pathways, particularly in the lung and other organs, such as the heart, contributes to a burst of cytokine release, which predisposes to significant tissue damage, loss of function, and mortality. The receptor for advanced glycation end products (RAGE) binds damage-associated molecular patterns is expressed in the lung and heart, and in priming organs, such as the blood vessels (in diabetes) and adipose tissue (in obesity), and transduces the pathological signals emitted by damage-associated molecular patterns. It is proposed that damage-associated molecular pattern-RAGE enrichment in these priming tissues, and in the lungs and heart during active infection, contributes to the widespread tissue damage induced by SARS-CoV-2. Accordingly, the RAGE axis might play seminal roles in and be a target for therapeutic intervention in SARS-CoV-2 infection.

Download Full-text

TLRs as a Promise Target Along With Immune Checkpoint Against Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.611444 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lin Cui ◽

Xiuqing Wang ◽

Dekai Zhang

Keyword(s):

Gastric Cancer ◽

Pattern Recognition ◽

Immune Responses ◽

Therapeutic Agents ◽

Pattern Recognition Receptors ◽

Innate Immune ◽

Therapeutic Approaches ◽

The World ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

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.

Download Full-text

Pattern recognition receptors in GtoPdb v.2021.3

IUPHAR/BPS Guide to Pharmacology CITE ◽

10.2218/gtopdb/f302/2021.3 ◽

2021 ◽

Vol 2021 (3) ◽

Author(s):

Clare Bryant ◽

Tom P. Monie

Keyword(s):

Pattern Recognition ◽

Cell Attachment ◽

Pattern Recognition Receptors ◽

Interferon Response ◽

Type I ◽

Intracellular Proteins ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns ◽

Microbial Agents ◽

Oligomerization Domain

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)

Download Full-text

Pattern recognition receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

IUPHAR/BPS Guide to Pharmacology CITE ◽

10.2218/gtopdb/f302/2019.4 ◽

2019 ◽

Vol 2019 (4) ◽

Cited By ~ 1

Author(s):

Clare Bryant ◽

Tom P. Monie

Keyword(s):

Pattern Recognition ◽

Cell Attachment ◽

Pattern Recognition Receptors ◽

Interferon Response ◽

Type I ◽

Intracellular Proteins ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns ◽

Microbial Agents ◽

Oligomerization Domain

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)

Download Full-text