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 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 Innate Immune Regulation by Toll-Like Receptors in the Brain

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Carina Mallard
Keyword(s):  
Immune Regulation ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptors ◽  
Receptor Ligands ◽  
Health And Disease ◽  
Cerebral Inflammation ◽  
The Brain

The innate immune system plays an important role in cerebral health and disease. In recent years the role of innate immune regulation by toll-like receptors in the brain has been highlighted. In this paper the expression of toll-like receptors and endogenous toll-like receptor ligands in the brain and their role in cerebral ischemia will be discussed. Further, the ability of systemic toll-like receptor ligands to induce cerebral inflammation will be reviewed. Finally, the capacity of toll-like receptors to both increase (sensitization) and decrease (preconditioning/tolerance) the vulnerability of the brain to damage will be disclosed. Studies investigating the role of toll-like receptors in the developing brain will be emphasized.

scholarly journals Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension

2014 ◽  
Vol 306 (2) ◽  
pp. H184-H196 ◽  
Author(s):  
Cameron G. McCarthy ◽  
Styliani Goulopoulou ◽  
Camilla F. Wenceslau ◽  
Kathryn Spitler ◽  
Takayuki Matsumoto ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cell Injury ◽  
Receptor Activation ◽  
Innate Immune ◽  
Immune System Activation ◽  
System Activation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Low-grade systemic inflammation is a common manifestation of hypertension; however, the exact mechanisms that initiate this pathophysiological response, thereby contributing to further increases in blood pressure, are not well understood. Aberrant vascular inflammation and reactivity via activation of the innate immune system may be the first step in the pathogenesis of hypertension. One of the functions of the innate immune system is to recognize and respond to danger. Danger signals can arise from not only pathogenic stimuli but also endogenous molecules released following cell injury and/or death [damage-associated molecular patterns (DAMPs)]. In the short-term, activation of the innate immune system is beneficial in the vasculature by providing cytoprotective mechanisms and facilitating tissue repair following injury or infection. However, sustained or excessive immune system activation, such as in autoimmune diseases, may be deleterious and can lead to maladaptive, irreversible changes to vascular structure and function. An initial source of DAMPs that enter the circulation to activate the innate immune system could arise from modest elevations in peripheral vascular resistance. These stimuli could subsequently lead to ischemic- or pressure-induced events aggravating further cell injury and/or death, providing more DAMPs for innate immune system activation. This review will address and critically evaluate the current literature on the role of the innate immune system in hypertension pathogenesis. The role of Toll-like receptor activation on somatic cells of the vasculature in response to the release of DAMPs and the consequences of this activation on inflammation, vasoreactivity, and vascular remodeling will be specifically discussed.

scholarly journals Pathogen Recognition by the Long Pentraxin PTX3

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Moalli ◽  
Sebastien Jaillon ◽  
Antonio Inforzato ◽  
Marina Sironi ◽  
Barbara Bottazzi ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Innate Immune System ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Pathogen Recognition ◽  
Evolutionarily Conserved ◽  
Infection And Inflammation ◽  
Molecular Patterns

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.

scholarly journals The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Mark Farrugia ◽  
Byron Baron
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
The Self ◽  
Sterile Inflammation ◽  
Molecular Signatures ◽  
Toll Like Receptors ◽  
Recognition Mechanism ◽  
Self Recognition

Toll-like receptors (TLRs), part of the innate immune system that recognises molecular signatures, are important in the recognition of pathogenic components. However, when specific cellular contexts develop in which TLRs are inappropriately activated by self-components, this may lead to sterile inflammation and result in the occurrence of autoimmunity. This review analyses the available data regarding TLR biochemistry, the specific mechanisms which are brought about by TLR activation, and the importance of these mechanisms in the light of any existing and potential therapies in the field of autoimmunity.

scholarly journals 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

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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