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

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.

scholarly journals Toll-like receptors and hypertension

2014 ◽  
Vol 307 (5) ◽  
pp. R501-R504 ◽  
Author(s):  
Madhu V. Singh ◽  
François M. Abboud
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Expression Patterns ◽  
Adaptor Proteins ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Cardiovascular Damage ◽  
Inflammatory Processes ◽  
Molecular Patterns

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.

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

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.

Das Komplementsystem

2012 ◽  
Vol 32 (04) ◽  
pp. 276-285 ◽  
Author(s):  
V. Frauenknecht ◽  
V. Schroeder
Keyword(s):  
Coronary Artery Disease ◽  
Complement System ◽  
Innate Immune System ◽  
Innate Immune ◽  
The Other ◽  
Atherosclerotic Plaques ◽  
Inflammatory Processes ◽  
Artery Disease ◽  
The Complement System ◽  
Novel Therapeutic

SummaryAtherosclerotic diseases such as coronary artery disease and ischaemic stroke are caused by chronic inflammation in arterial vessel walls. The complement system is part of the innate immune system. It is involved in many processes contributing to onset and development of atherosclerotic plaques up to the final stage of acute thrombotic events. This is due to its prominent role in inflammatory processes. In addition, there is increasing evidence that interactions between complement and coagulation provide a link between inflammation and thrombosis. On the other hand, the complement system also has an atheroprotective function through the clearance of apoptotic material.The knowledge of these complex mechanisms will become increasingly important, also for clinicians, since it may lead to novel therapeutic and diagnostic options. Therapies targeting the complement system have the potential to reduce tissue damage caused by acute ischaemic events. Whether early anti-inflammatory and anti-complement therapy may be able to prevent atherosclerosis, remains a hot topic for research.

scholarly journals Therapeutic Interventions into Innate Immune Diseases by Means of Aptamers

Pharmaceutics ◽  
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.

scholarly journals Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity

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.

Bacterial cell wall macroamphiphiles: Pathogen-/microbe-associated molecular patterns detected by mammalian innate immune system

Biochimie ◽  
2013 ◽  
Vol 95 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Aurélie Ray ◽  
Marlène Cot ◽  
Germain Puzo ◽  
Martine Gilleron ◽  
Jérôme Nigou
Keyword(s):  
Cell Wall ◽  
Immune System ◽  
Bacterial Cell ◽  
Innate Immune System ◽  
Bacterial Cell Wall ◽  
Innate Immune ◽  
Molecular Patterns

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
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.

scholarly journals In Vivo Discrimination of Type 3 Secretion System-Positive and -Negative Pseudomonas aeruginosa via a Caspase-1-Dependent Pathway

2010 ◽  
Vol 78 (11) ◽  
pp. 4744-4753 ◽  
Author(s):  
Tamding Wangdi ◽  
Lilia A. Mijares ◽  
Barbara I. Kazmierczak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune System ◽  
Innate Immune System ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Secretion Systems ◽  
Caspase 1 ◽  
Molecular Patterns ◽  
Type 3

ABSTRACT Microbe-associated molecular patterns are recognized by Toll-like receptors of the innate immune system. This recognition enables a rapid response to potential pathogens but does not clearly provide a way for the innate immune system to discriminate between virulent and avirulent microbes. We find that pulmonary infection of mice with type 3 translocation-competent Pseudomonas aeruginosa triggers a rapid inflammatory response, while infection with isogenic translocation-deficient mutants does not. Discrimination between translocon-positive and -negative bacteria requires caspase-1 activity in bone marrow-derived cells and interleukin-1 receptor signaling. Thus, the activation of caspase-1 by bacteria expressing type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.

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