NLRP6 Induces Pyroptosis by Activation of Caspase-1 in Gingival Fibroblasts

2018 ◽  
Vol 97 (12) ◽  
pp. 1391-1398 ◽  
Author(s):  
W. Liu ◽  
J. Liu ◽  
W. Wang ◽  
Y. Wang ◽  
X. Ouyang
Keyword(s):  
Innate Immune ◽  
Gingival Tissue ◽  
Gingival Fibroblasts ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Commensal Bacterium ◽  
Caspase 1 ◽  
Proinflammatory Mediators ◽  
First Time ◽  
Receptor Family

NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, has been reported to participate in inflammasome formation. Activation of inflammasome triggers a caspase-1–dependent programming cell death called pyroptosis. However, whether NLRP6 induces pyroptosis has not been investigated. In this study, we showed that NLRP6 overexpression activated caspase-1 and gasdermin-D and then induced pyroptosis of human gingival fibroblasts, resulting in release of proinflammatory mediators interleukin (IL)–1β and IL-18. Moreover, NLRP6 was highly expressed in gingival tissue of periodontitis compared with healthy controls. Porphyromonas gingivalis, which is a commensal bacterium and has periodontopathic potential, induced pyroptosis of gingival fibroblasts by activation of NLRP6. Together, we, for the first time, identified that NLRP6 could induce pyroptosis of gingival fibroblasts by activation of caspase-1 and may play a role in periodontitis.

scholarly journals Receptors in the induction of the plant innate immunity

2021 ◽  
Author(s):  
Tian-Ying Yu ◽  
Meng-Kun Sun ◽  
Li-Kun Liang
Keyword(s):  
Immune Responses ◽  
Innate Immune System ◽  
Effector Proteins ◽  
Innate Immune ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Effector Triggered Immunity ◽  
Growth Development ◽  
Immune Pathway ◽  
Molecular Patterns

Plants adjust amplitude and duration of immune responses via different strategies to maintain growth, development and resistance to pathogens. Pathogen-associated molecular patterns (PAMPs)-triggered immunity (PTI) and effector-triggered immunity (ETI) play vital roles. PRRs (pattern recognition receptors), comprising a large number of receptor-like protein kinases (RLKs) and receptor-like proteins (RLPs), recognize related ligands and trigger immunity. PTI is the first layer of the innate immune system, and it recognizes PAMPs at plasma membrane to prevent infection. However, pathogens exploit effector proteins to bypass or directly inhibit the PTI immune pathway. Consistently, plants have evolved intracellular nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins to detect pathogenic effectors and trigger a hypersensitive response to activate ETI. PTI and ETI work together to protect plants from infection of virus and other pathogens. Diverse receptors and the corresponding ligands, especially several pairs of well-studied receptors and ligands in PTI immunity, are reviewed to illustrate the dynamic process of PTI response here.

scholarly journals Inflammasome Components Coordinate Autophagy and Pyroptosis as Macrophage Responses to Infection

mBio ◽  
2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Brenda G. Byrne ◽  
Jean-Francois Dubuisson ◽  
Amrita D. Joshi ◽  
Jenny J. Persson ◽  
Michele S. Swanson
Keyword(s):  
Cell Death ◽  
Legionella Pneumophila ◽  
Nucleotide Binding ◽  
Binding Domain ◽  
Mouse Genetics ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Caspase 1 ◽  
Primary Mouse ◽  
Mouse Macrophages

ABSTRACTWhen microbes contaminate the macrophage cytoplasm, leukocytes undergo a proinflammatory death that is initiated by nucleotide-binding-domain-, leucine-rich-repeat-containing proteins (NLR proteins) that bind and activate caspase-1. We report that these inflammasome components also regulate autophagy, a vesicular pathway to eliminate cytosolic debris. In response to infection with flagellateLegionella pneumophila, C57BL/6J mouse macrophages equipped with caspase-1 and the NLR proteins NAIP5 and NLRC4 stimulated autophagosome turnover. A second trigger of inflammasome assembly, K+efflux, also rapidly activated autophagy in macrophages that produced caspase-1. Autophagy protects infected macrophages from pyroptosis, since caspase-1-dependent cell death occurred more frequently when autophagy was dampened pharmacologically by either 3-methyladenine or an inhibitor of the Atg4 protease. Accordingly, in addition to coordinating pyroptosis, both (pro-) caspase-1 protein and NLR components of inflammasomes equip macrophages to recruit autophagy, a disposal pathway that raises the threshold of contaminants necessary to trigger proinflammatory leukocyte death.IMPORTANCEAn exciting development in the innate-immunity field is the recognition that macrophages enlist autophagy to protect their cytoplasm from infection. Nutrient deprivation has long been known to induce autophagy; how infection triggers this disposal pathway is an active area of research. Autophagy is encountered by many of the intracellular pathogens that are known to trigger pyroptosis, an inflammatory cell death initiated when nucleotide-binding-domain-, leucine-rich-repeat-containing proteins (NLR proteins) activate caspase-1 within inflammasome complexes. Therefore, we tested the hypothesis that NLR proteins and caspase-1 also coordinate autophagy as a barrier to cytosolic infection. By exploiting classical bacterial and mouse genetics and kinetic assays of autophagy, we demonstrate for the first time that, when confronted with cytosolic contamination, primary mouse macrophages rely not only on the NLR proteins NAIP5 and NLRC4 but also on (pro-)caspase-1 protein to mount a rapid autophagic response that wards off proinflammatory cell death.

scholarly journals Development of an in vitro assay for the detection of polymerization of the pyrin domain of ASC

BioTechniques ◽  
2021 ◽  
Author(s):  
Ian P Bresch ◽  
Dominik A Machtens ◽  
Thomas F Reubold ◽  
Susanne Eschenburg
Keyword(s):  
Protein Complexes ◽  
In Vitro Assay ◽  
Innate Immune ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Vitro Assay ◽  
Microscale Thermophoresis ◽  
Pyrin Domain ◽  
Polymerization Behavior

Multicomponent protein complexes called inflammasomes play a major role in the innate immune system by activating proinflammatory cytokines and promoting a highly inflammatory form of programmed cell death, called pyroptosis. A hallmark of the function of the nucleotide-binding domain, leucine-rich repeat and NLRP3-mediated inflammasome assembly is the polymerization of ASC into large filaments. The ASC filaments recruit and activate procaspase-1 by induced proximity. We developed an in vitro assay for monitoring the polymerization of the pyrin domain of ASC by microscale thermophoresis. We have validated the assay by analyzing the effects of buffer conditions, mutations of ASC and the use of seeds on the polymerization behavior of ASC.

scholarly journals The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

2021 ◽  
Vol 9 (6) ◽  
pp. 1324
Author(s):  
Fernanda Raya Tonetti ◽  
Mikado Tomokiyo ◽  
Ramiro Ortiz Moyano ◽  
Sandra Quilodrán-Vega ◽  
Hikari Yamamuro ◽  
...  
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Innate Immune Response ◽  
Pneumococcal Infection ◽  
Innate Immune ◽  
Nasal Administration ◽  
Commensal Bacterium ◽  
Beneficial Effects ◽  
Immunological Mechanisms ◽  
Immunomodulatory Properties

Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

scholarly journals Role of the Inflammasome, IL-1β, and IL-18 in Bacterial Infections

2011 ◽  
Vol 11 ◽  
pp. 2037-2050 ◽  
Author(s):  
Manoranjan Sahoo ◽  
Ivonne Ceballos-Olvera ◽  
Laura del Barrio ◽  
Fabio Re
Keyword(s):  
Bacterial Infections ◽  
Innate Immune ◽  
Host Responses ◽  
Inflammasome Activation ◽  
Different Types ◽  
Molecular Aspects ◽  
Immune Pathway ◽  
Innate Immune Pathway ◽  
Receptor Family

The inflammasome is an important innate immune pathway that regulates at least two host responses protective against infections: (1) secretion of the proinflammatory cytokines IL-1βand IL-18 and (2) induction of pyroptosis, a form of cell death. Inflammasomes, of which different types have been identified, are multiprotein complexes containing pattern recognition receptors belonging to the Nod-like receptor family or the PYHIN family and the protease caspase-1. The molecular aspects involved in the activation of different inflammasomes by various pathogens are being rapidly elucidated, and their role during infections is being characterized. Production of IL-1βand IL-18 and induction of pyroptosis of the infected cell have been shown to be protective against many infectious agents. Here, we review the recent literature concerning inflammasome activation in the context of bacterial infections and identify important questions to be answered in the future.

scholarly journals LRR protein RNH1 inhibits inflammasome activation through proteasome-mediated degradation of Caspase-1 and is associated with adverse clinical outcomes in COVID-19 patients.

2021 ◽  
Author(s):  
Giuseppe Bombaci ◽  
Mayuresh A Sarangdhar ◽  
Nicola Andina ◽  
Aubry Tardivel ◽  
Eric Chi-Wang Yu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Neutrophil Infiltration ◽  
Inflammasome Activation ◽  
Ribonuclease Inhibitor ◽  
Protein Levels ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Underlying Mechanisms ◽  
Lrr Protein ◽  
Receptor Family

Inflammasomes are cytosolic innate immune sensors that, upon activation, induce caspase-1 mediated inflammation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and is also detrimental in COVID-19 infection. However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine rich repeat (LRR) protein Ribonuclease inhibitor (RNH1), which shares homology with LRRs of NOD-like receptor family pyrin domain (PYD)-containing (NLRP) proteins, attenuates inflammasome activation. Mechanistically, RNH1 decreased pro-IL1b expression and induced proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and LPS-induced endotoxemia, which are dependent on caspase-1, respectively showed increased neutrophil infiltration and lethality in Rnh1-/- mice compared to WT mice. Further, RNH1 protein levels were negatively correlated with inflammation and disease severity in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.

scholarly journals Lessons in effector and NLR biology of plant-microbe systems

2017 ◽  
Author(s):  
Aleksandra Białas ◽  
Erin K. Zess ◽  
Juan Carlos De la Concepcion ◽  
Marina Franceschetti ◽  
Helen G. Pennington ◽  
...  
Keyword(s):  
Plant Physiology ◽  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Molecular Mechanisms ◽  
Rice Blast Fungus ◽  
Leucine Rich Repeat ◽  
Nucleotide Binding Domain ◽  
Immune Receptors ◽  
Microbe Interactions ◽  
Host Infection

A diversity of plant-associated organisms secrete effectors—proteins and metabolites that modulate plant physiology to favor host infection and colonization. However, effectors can also activate plant immune receptors, notably nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins, enabling plants to fight off invading organisms. This interplay between effectors, their host targets, and the matching immune receptors is shaped by intricate molecular mechanisms and exceptionally dynamic coevolution. In this article, we focus on three effectors, AVR-Pik, AVR-Pia, and AVR-Pii, from the rice blast fungus Magnaporthe oryzae (syn. Pyricularia oryzae), and their corresponding rice NLR immune receptors, Pik, Pia, and Pii, to highlight general concepts of plant-microbe interactions. We draw 12 lessons in effector and NLR biology that have emerged from studying these three little effectors and are broadly applicable to other plant-microbe systems.

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