scholarly journals The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

2021 ◽  
Vol 22 (3) ◽  
pp. 1271
Author(s):  
Laura Urwanisch ◽  
Michela Luciano ◽  
Jutta Horejs-Hoeck
Keyword(s):  
Nlrp3 Inflammasome ◽  
Innate Immune System ◽  
Inflammatory Cell ◽  
Current Knowledge ◽  
Innate Immune ◽  
Leukemic Cells ◽  
Different Types ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

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 Targeting Innate Immunity to Combat Cutaneous Stress: The Vitiligo Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Katia Boniface ◽  
Thierry Passeron ◽  
Julien Seneschal ◽  
Meri K. Tulic
Keyword(s):  
Immune Response ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Danger Signals ◽  
Multiple Factors ◽  
Autoimmune Condition ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed.

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.

scholarly journals The Role of Peptide Signals Hidden in the Structure of Functional Proteins in Plant Immune Responses

2019 ◽  
Vol 20 (18) ◽  
pp. 4343 ◽  
Author(s):  
Irina Lyapina ◽  
Anna Filippova ◽  
Igor Fesenko
Keyword(s):  
Immune Responses ◽  
Defense Responses ◽  
Innate Immune ◽  
Functional Protein ◽  
Diverse Range ◽  
Peptide Signals ◽  
Plant Pathogen Interactions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Plants have evolved a sophisticated innate immune system to cope with a diverse range of phytopathogens and insect herbivores. Plasma-membrane-localized pattern recognition receptors (PRRs), such as receptor-like kinases (RLK), recognize special signals, pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), and trigger immune responses. A growing body of evidence shows that many peptides hidden in both plant and pathogen functional protein sequences belong to the group of such immune signals. However, the origin, evolution, and release mechanisms of peptide sequences from functional and nonfunctional protein precursors, known as cryptic peptides, are largely unknown. Various special proteases, such as metacaspase or subtilisin-like proteases, are involved in the release of such peptides upon activation during defense responses. In this review, we discuss the roles of cryptic peptide sequences hidden in the structure of functional proteins in plant defense and plant-pathogen interactions.

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 Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard Felix Kraus ◽  
Michael Andreas Gruber
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Immune Defense ◽  
Innate Immune ◽  
Human Organism ◽  
Polymorphonuclear Cells ◽  
Target Tissue ◽  
First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

scholarly journals Emerging Role of the Inflammasome and Pyroptosis in Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1064
Author(s):  
Carmen De Miguel ◽  
Pablo Pelegrín ◽  
Alberto Baroja-Mazo ◽  
Santiago Cuevas
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Nlrp3 Inflammasome ◽  
Organ Damage ◽  
Subsequent Formation ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Inflammasomes are components of the innate immune response that have recently emerged as crucial controllers of tissue homeostasis. In particular, the nucleotide-binding domain, leucine-rich-containing (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a complex platform involved in the activation of caspase-1 and the maturation of interleukin (IL)-1β and IL-18, which are mainly released via pyroptosis. Pyroptosis is a caspase-1-dependent type of cell death that is mediated by the cleavage of gasdermin D and the subsequent formation of structurally stable pores in the cell membrane. Through these pores formed by gasdermin proteins cytosolic contents are released into the extracellular space and act as damage-associated molecular patterns, which are pro-inflammatory signals. Inflammation is a main contributor to the development of hypertension and it also is known to stimulate fibrosis and end-organ damage. Patients with essential hypertension and animal models of hypertension exhibit elevated levels of circulating IL-1β. Downregulation of the expression of key components of the NLRP3 inflammasome delays the development of hypertension and pharmacological inhibition of this inflammasome leads to reduced blood pressure in animal models and humans. Although the relationship between pyroptosis and hypertension is not well established yet, pyroptosis has been associated with renal and cardiovascular diseases, instances where high blood pressure is a critical risk factor. In this review, we summarize the recent literature addressing the role of pyroptosis and the inflammasome in the development of hypertension and discuss the potential use of approaches targeting this pathway as future anti-hypertensive strategies.

scholarly journals Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Patrícia R S Rodrigues ◽  
Aljawharah Alrubayyi ◽  
Ellie Pring ◽  
Valentina M T Bart ◽  
Ruth Jones ◽  
...  
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Innate Immunology ◽  
Viral Pathogen ◽  
Health Crisis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.

scholarly journals For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Sandra Zivkovic ◽  
Maryam Ayazi ◽  
Grace Hammel ◽  
Yi Ren
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Innate Immune ◽  
Traumatic Spinal Cord Injury ◽  
Injured Spinal Cord ◽  
Cord Injury ◽  
Molecular Patterns

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.

scholarly journals Cytosolic Sensors for Pathogenic Viral and Bacterial Nucleic Acids in Fish

2020 ◽  
Vol 21 (19) ◽  
pp. 7289
Author(s):  
Miriam Mojzesz ◽  
Krzysztof Rakus ◽  
Magdalena Chadzinska ◽  
Kentaro Nakagami ◽  
Gouranga Biswas ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nucleic Acids ◽  
Current Knowledge ◽  
Innate Immune ◽  
Rna Helicases ◽  
Protein Kinase R ◽  
Evolutionarily Conserved ◽  
Different Types ◽  
Molecular Patterns ◽  
Inducible Gene

Recognition of the non-self signature of invading pathogens is a crucial step for the initiation of the innate immune mechanisms of the host. The host response to viral and bacterial infection involves sets of pattern recognition receptors (PRRs), which bind evolutionarily conserved pathogen structures, known as pathogen-associated molecular patterns (PAMPs). Recent advances in the identification of different types of PRRs in teleost fish revealed a number of cytosolic sensors for recognition of viral and bacterial nucleic acids. These are DExD/H-box RNA helicases including a group of well-characterized retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and non-RLR DExD/H-box RNA helicases (e.g., DDX1, DDX3, DHX9, DDX21, DHX36 and DDX41) both involved in recognition of viral RNAs. Another group of PRRs includes cytosolic DNA sensors (CDSs), such as cGAS and LSm14A involved in recognition of viral and intracellular bacterial dsDNAs. Moreover, dsRNA-sensing protein kinase R (PKR), which has a role in antiviral immune responses in higher vertebrates, has been identified in fish. Additionally, fish possess a novel PKR-like protein kinase containing Z-DNA binding domain, known as PKZ. Here, we review the current knowledge concerning cytosolic sensors for recognition of viral and bacterial nucleic acids in teleosts.

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