Toll-like receptors and hypertension

Hypertension and associated inflammatory processes that accelerate cardiovascular damage are regulated by the innate immune system. Toll-like receptors (TLR) are major components of the innate immune system that recognize endogenous damage-associated molecular patterns to activate prominent inflammatory signaling including activation of nuclear factor-κB (NF-κB). However, the role of TLR in the etiology of hypertension is not well understood. TLR signaling is dependent on adaptor proteins that, along with the TLR expression patterns, confer specificity of the inflammatory response and its pathological targets. Here we review the conceptual framework of how TLR and their adaptor proteins may differentially affect hypertension and cardiac hypertrophy by different stimuli.

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Role of Toll-like receptors in liver health and disease

Clinical Science ◽

10.1042/cs20110065 ◽

2011 ◽

Vol 121 (10) ◽

pp. 415-426 ◽

Cited By ~ 48

Author(s):

Ruth Broering ◽

Mengji Lu ◽

Joerg F. Schlaak

Keyword(s):

Immune System ◽

Liver Disease ◽

Innate Immune System ◽

Innate Immune ◽

Toll Like Receptors ◽

Evolutionarily Conserved ◽

Liver Health ◽

Health And Disease ◽

Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

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P789TLR-4 expression predicts mortality in patients with acute heart failure

European Heart Journal ◽

10.1093/eurheartj/ehz747.0388 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K A Krychtiuk ◽

M Lenz ◽

K Huber ◽

C Hengstenberg ◽

J Wojta ◽

...

Keyword(s):

Heart Failure ◽

Critically Ill ◽

Acute Heart Failure ◽

Innate Immune System ◽

Prospective Observational Study ◽

Expression Patterns ◽

Innate Immune ◽

Inflammatory Processes ◽

Molecular Patterns ◽

Inflammatory System

Abstract Background Inflammation is regarded as an important trigger for disease progression in heart failure (HF) and activation of the inflammatory system was implicated in the pathophysiology of acute heart failure (AHF). Toll-like receptors (TLRs) play an important role in acute inflammatory processes in critically ill patients by binding to pathogen associated molecular patterns (PAMP) and danger associated molecular patterns (DAMP). However, it is not known whether the expression patterns of TLRs on neutrophils and monocytes are associated with outcome in patients with severe AHF requiring intensive care unit (ICU) admission. The aim of this prospective, observational study was to analyze whether TLR-expression on monocytes or neutrophils is associated with 30-day survival in patients with severe AHF. Methods We included 84 patients with severe AHF admitted to a cardiac ICU. Blood was taken at admission and mean fluorescence activity (MFI) of TLR-2, TLR-4 and TLR-9 on monocytes and neutrophils was analyzed by flow cytometry. Results Median age was 64 (IQR 48–74) years and 76.2% of patients were male. Median NT-proBNP was 4941 (IQR 1298–12273) pg/mL and 30-day mortality was 33.3%. TLR-4 expression on monocytes in survivors (740 IQR 694–854) was significantly lower than in non-survivors (871 IQR 723–979; p<0.05). TLR-2 and TLR-9 expression on monocytes and TLR expression on neutrophils was not associated with survival. TLR-4 expression on monocytes was significantly associated with survival independent of age, sex, creatinine and NT-proBNP levels. Conclusion Monocyte TLR-4 expression predicts mortality in patients admitted to a cardiac ICU for severe acute heart failure. This suggests that activation of the innate immune system by TLR-binding of DAMPS may play a significant role in critically ill acute heart failure patients.

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Toll-like Receptors (TLRs), NOD-like Receptors (NLRs) and RIG-I-like Receptors (RLRs) in Innate Immunity. TLRs, NLRs and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms222413397 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13397

Author(s):

Katarzyna Wicherska-Pawłowska ◽

Tomasz Wróbel ◽

Justyna Rybka

Keyword(s):

Immune System ◽

Immune Cells ◽

Innate Immune System ◽

Intracellular Signaling ◽

Innate Immune ◽

Toll Like Receptors ◽

Transmembrane Receptors ◽

Cancer Immunotherapies ◽

Molecular Patterns ◽

Cancer Immunosurveillance

The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases.

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The activation of the hepatic innate immune system by siRNA is controlled by chemical modifications and may involve endosomal Toll-like receptors

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1246501 ◽

2010 ◽

Vol 48 (01) ◽

Author(s):

R Bröring ◽

M John ◽

K Kleinehr ◽

JP Sowa ◽

A Bucchi ◽

...

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Toll Like Receptors ◽

Chemical Modifications

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NOD-Like Receptors: Guards of Cellular Homeostasis Perturbation during Infection

International Journal of Molecular Sciences ◽

10.3390/ijms22136714 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6714

Author(s):

Gang Pei ◽

Anca Dorhoi

Keyword(s):

Immune System ◽

Innate Immune System ◽

Current Knowledge ◽

Protein Translation ◽

Innate Immune ◽

Cellular Homeostasis ◽

Translation Block ◽

Cytoskeleton Disruption ◽

Molecular Patterns ◽

Fine Tune

The innate immune system relies on families of pattern recognition receptors (PRRs) that detect distinct conserved molecular motifs from microbes to initiate antimicrobial responses. Activation of PRRs triggers a series of signaling cascades, leading to the release of pro-inflammatory cytokines, chemokines and antimicrobials, thereby contributing to the early host defense against microbes and regulating adaptive immunity. Additionally, PRRs can detect perturbation of cellular homeostasis caused by pathogens and fine-tune the immune responses. Among PRRs, nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) have attracted particular interest in the context of cellular stress-induced inflammation during infection. Recently, mechanistic insights into the monitoring of cellular homeostasis perturbation by NLRs have been provided. We summarize the current knowledge about the disruption of cellular homeostasis by pathogens and focus on NLRs as innate immune sensors for its detection. We highlight the mechanisms employed by various pathogens to elicit cytoskeleton disruption, organelle stress as well as protein translation block, point out exemplary NLRs that guard cellular homeostasis during infection and introduce the concept of stress-associated molecular patterns (SAMPs). We postulate that integration of information about microbial patterns, danger signals, and SAMPs enables the innate immune system with adequate plasticity and precision in elaborating responses to microbes of variable virulence.

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P0022INNATE IMMUNE RESPONSES ELICITED BY TOLL-LIKE RECEPTORS ARE POSSIBLY INVOLVED IN THE PATHOGENESIS OF NEPHROTIC SYNDROME

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0022 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Eriko Tanaka ◽

Ichiro Hada ◽

Naoaki Mikami ◽

Kunimasa Yan

Keyword(s):

Innate Immunity ◽

Nephrotic Syndrome ◽

Immune System ◽

Innate Immune System ◽

Expression Profiles ◽

Kidney Tissue ◽

Innate Immune ◽

Rna Expression ◽

Toll Like Receptors ◽

Tissue Samples

Abstract Background and Aims Pathogenesis of idiopathic nephrotic syndrome (INS) is yet to be fully elucidated. Immunological disorders are reported to be involved in the etiology of INS. Due to the efficacy of immunosuppressant agents such as calcineurin inhibitor and rituximab in treating nephrotic syndrome, aberrant activation of the acquired immune system through T and B cells are considered to be the underlying pathogenic mechanisms of INS. Nevertheless, there is a possibility that the innate immune system plays a key role in INS pathogenesis. This study aims to investigate the involvement of innate immunity in INS pathogenesis by examining the expressions of toll-like receptors (TLRs). Method Kidney tissue samples from two INS patients were collected at two points of time: the first biopsy was performed during nephrosis and the second during remission. Total RNA was extracted from the kidney tissue samples, and RNA-sequencing was performed to investigate RNA expression profiles. The differences between RNA expression profiles of TLRs and molecules related to TLR pathways in the tissue samples collected during nephrosis and remission were analyzed. Results There was a significant decrease in RNA expression of TLR9 and TLR10 during remission compared to nephrosis: fold change in each patient was -2.12 and -2.12 for TLR9, and -2.51 and -2.09 for TLR10. RNA expression of TLR8 also decreased: fold change in each patient was -1.19 and -1.75. There were no significant changes in the RNA expression profiles of TLR1, 2, 3, 4, 5, 6, and 7. In addition, there were no differences in the RNA expression profiles of MYD88, IRAK family, and TRAF family molecules that are associated with TLR pathways. However, RNA expressions of IL6, IL1B, IL12B, and TNF, as well as the cytokines controlled by TLR8 and TLR9 pathways, which were activated during nephrosis, disappeared or decreased during remission. Conclusion The involvement of the innate immune system in the pathogenesis of nephrotic syndrome has been suggested in some reports. Based on the fact that the onset or recurrence of nephrosis is triggered by non-specific viral infection, it is highly possible that innate immunity is involved in the pathogenesis of nephrotic syndrome. TLRs play a key role in innate immunity as they elicit the innate immune system after detecting pathogens, induce inflammatory cytokine production, and trigger signaling pathways that activate lymphocytes via maturation of dendritic cells. Specifically, TLR8, 9, and 10 mediate pathways of the first immune response to viral infections. Our study reveals that TLRs play a pivotal role in innate immunity associated with renal tissue during the onset of nephrosis.

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Therapeutic Interventions into Innate Immune Diseases by Means of Aptamers

Pharmaceutics ◽

10.3390/pharmaceutics12100955 ◽

2020 ◽

Vol 12 (10) ◽

pp. 955

Author(s):

Farzana Yasmeen ◽

Hana Seo ◽

Nasir Javaid ◽

Moon Suk Kim ◽

Sangdun Choi

Keyword(s):

Pattern Recognition ◽

Immune System ◽

Crucial Role ◽

Innate Immune System ◽

Innate Immune ◽

Therapeutic Interventions ◽

Immune System Diseases ◽

Target Molecules ◽

Molecular Patterns ◽

Recognition Receptor

The immune system plays a crucial role in the body’s defense system against various pathogens, such as bacteria, viruses, and parasites, as well as recognizes non-self- and self-molecules. The innate immune system is composed of special receptors known as pattern recognition receptors, which play a crucial role in the identification of pathogen-associated molecular patterns from diverse microorganisms. Any disequilibrium in the activation of a particular pattern recognition receptor leads to various inflammatory, autoimmune, or immunodeficiency diseases. Aptamers are short single-stranded deoxyribonucleic acid or ribonucleic acid molecules, also termed “chemical antibodies,” which have tremendous specificity and affinity for their target molecules. Their features, such as stability, low immunogenicity, ease of manufacturing, and facile screening against a target, make them preferable as therapeutics. Immune-system–targeting aptamers have a great potential as a targeted therapeutic strategy against immune diseases. This review summarizes components of the innate immune system, aptamer production, pharmacokinetic characteristics of aptamers, and aptamers related to innate-immune-system diseases.

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Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity

Frontiers in Neurology ◽

10.3389/fneur.2020.598894 ◽

2020 ◽

Vol 11 ◽

Author(s):

Mingqin Zhu ◽

Yuetao Ma ◽

Anastasia Zekeridou ◽

Vanda A. Lennon

Keyword(s):

Immune System ◽

Innate Immune System ◽

Protein Complexes ◽

Innate Immune ◽

Neurological Symptoms ◽

Autoimmune Response ◽

Tnf Α ◽

Bladder Instillation ◽

Molecular Patterns ◽

Symptoms And Signs

Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is discovered. We describe four patients whose neurological symptoms were precipitated by potent innate immune system challenges: bladder instillation of BCG, tick bite and an “alternative cancer therapy” with bacterial extracts and TNF-α. We hypothesize that a tumor-initiated autoimmune response (evidenced by autoantibody profiles), pre-dating the immune system challenge, was unmasked or amplified in these patients by cytokines released systemically from innate immune cells activated by microbial pathogen-associated molecular patterns (PAMPs). The resultant upregulation of cognate onconeural peptides as MHC1 protein complexes on neural cell surfaces would render those cells susceptible to killing by CD8+ T cells, thus precipitating the patient's neurological symptoms.

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