Noncanonical inflammasomes: Antimicrobial defense that does not play by the rules

Crowley, Shauna M.; Vallance, Bruce A.; Knodler, Leigh A.

doi:10.1111/cmi.12730

Cited by 21 publications

(23 citation statements)

References 74 publications

(221 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, colonic tissue explants from C. rodentium -infected caspase-11 -deficient mice also had decreased IL-18 secretion ( 160 ). This caspase-11-dependent IL-18 processing was proposed to occur in IEC, contrary to the caspase-1-dependent cleavage of IL-18 and IL-1β observed in myeloid cells ( 161 ).…”

Section: Inflammasomes and Cell Death: Pyroptosis And Apoptosismentioning

confidence: 72%

“…The importance of “canonical” and “non-canonical” inflammasomes may vary depending on the nature and characteristics of the pathogenic threat and the cell types involved. For example, upon challenge with flagellin-deficient Salmonella , caspase-1-deficient macrophages died in a similar manner to WT macrophages, whereas caspase-11-deficient macrophages were resistant to cell death ( 158 , 161 ). In contrast, both caspase-1 and caspase-11 were required for cell death in macrophages infected with WT Salmonella ( 158 ).…”

Section: Inflammasomes and Cell Death: Pyroptosis And Apoptosismentioning

confidence: 99%

See 1 more Smart Citation

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

2017

View full text Add to dashboard Cite

Pattern recognition receptors (PRR), such as NOD-like receptors (NLRs), sense conserved microbial signatures, and host danger signals leading to the coordination of appropriate immune responses. Upon activation, a subset of NLR initiate the assembly of a multimeric protein complex known as the inflammasome, which processes pro-inflammatory cytokines and mediates a specialized form of cell death known as pyroptosis. The identification of inflammasome-associated genes as inflammatory bowel disease susceptibility genes implicates a role for the inflammasome in intestinal inflammation. Despite the fact that the functional importance of inflammasomes within immune cells has been well established, the contribution of inflammasome expression in non-hematopoietic cells remains comparatively understudied. Given that intestinal epithelial cells (IEC) act as a barrier between the host and the intestinal microbiota, inflammasome expression by these cells is likely important for intestinal immune homeostasis. Accumulating evidence suggests that the inflammasome plays a key role in shaping epithelial responses at the host–lumen interface with many inflammasome components highly expressed by IEC. Recent studies have exposed functional roles of IEC inflammasomes in mucosal immune defense, inflammation, and tumorigenesis. In this review, we present the main features of the predominant inflammasomes and their effector mechanisms contributing to intestinal homeostasis and inflammation. We also discuss existing controversies in the field and open questions related to their implications in disease. A comprehensive understanding of the molecular basis of intestinal inflammasome signaling could hold therapeutic potential for clinical translation.

show abstract

Section: Inflammasomes and Cell Death: Pyroptosis And Apoptosismentioning

confidence: 72%

Section: Inflammasomes and Cell Death: Pyroptosis And Apoptosismentioning

confidence: 99%

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

2017

View full text Add to dashboard Cite

show abstract

“…The inflammasome has been shown to play a pivotal role in the inflammatory response by activating the inflammatory caspase caspase‐1, which induces pyroptosis and the secretion of the pro‐inflammatory cytokine IL‐1 β in macrophages. In these inflammasome studies, caspase‐11 was unexpectedly identified as a novel activator of caspase‐1, and the complex of caspase‐11 and intracellular LPS was referred to as the ‘non‐canonical inflammasome’, adding to the diversity of cytoplasmic innate immunity responses in macrophages . Recent studies have not only identified intracellular LPS as agonists of the non‐canonical inflammasome, but also demonstrated that inflammatory caspases, such as a mouse caspase‐11 and human caspase‐4/5, are direct molecular sensors of intracellular LPS and activate non‐canonical inflammasome responses .…”

Section: Discussionmentioning

confidence: 99%

“…In these inflammasome studies, caspase-11 was unexpectedly identified as a novel activator of caspase-1, and the complex of caspase-11 and intracellular LPS was referred to as the 'non-canonical inflammasome', 19 adding to the diversity of cytoplasmic innate immunity responses in macrophages. 86,87 Recent studies have not only identified intracellular LPS as agonists of the non-canonical inflammasome, 21,22 but also demonstrated that inflammatory caspases, such as a mouse caspase-11 and human caspase-4/5, are direct molecular sensors of intracellular LPS and activate non-canonical inflammasome responses. 23 Intracellular LPS released from the Gram-negative bacterium-containing vacuoles by GBP chr3 -mediated proteolysis are directly detected by caspases-4/5/11, and these caspases are oligomerized and activated, thereby inducing anti-pathogenic inflammatory responses by triggering pyroptosis and secretion of IL-1b and IL-18 in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses

2017

Immunology

182

216

View full text Add to dashboard Cite

SummaryInflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria stimulates an inflammatory response by macrophages. During the inflammatory response, extracellular LPS is recognized by Toll-like receptor 4, one of the pattern recognition receptors that activates inflammatory signalling pathways and leads to the production of inflammatory mediators. The innate immune response is also triggered by intracellular inflammasomes, and inflammasome activation induces pyroptosis and the secretion of pro-inflammatory cytokines such as interleukin-1b (IL-1b) and IL-18 by macrophages. Cysteine-aspartic protease (caspase)-11 and the human orthologues caspase-4/caspase-5 were recently identified as components of the 'non-canonical inflammasome' that senses intracellular LPS derived from Gram-negative bacteria during macrophage-mediated inflammatory responses. Direct recognition of intracellular LPS facilitates the rapid oligomerization of caspase-11/4/5, which results in pyroptosis and the secretion of IL-1b and IL-18. LPS is released into the cytoplasm from Gram-negative bacterium-containing vacuoles by small interferoninducible guanylate-binding proteins encoded on chromosome 3 (GBP chr3 )-mediated lysis of the vacuoles. In vivo studies have clearly shown that caspase-11 À/À mice are more resistant to endotoxic septic shock by excessive LPS challenge. Given the evidence, activation of caspase-11 non-canonical inflammasomes by intracellular LPS is distinct from canonical inflammasome activation and provides a new paradigm in macrophagemediated inflammatory responses.

show abstract

“…Other innate detection systems rely on canonical or non-canonical inflammasomes [13,14]. They are induced by PAMP or Danger-Associated Molecular Patterns (DAMP) and lead to the activation of the Caspase-1, which in turn cleaves precursor molecules (e.g., pro-IL-1β and pro-IL-18) to liberate active IL-1β and IL-18 in the infected or endangered microenvironment.…”

Section: Interplay Between Hbv and Innate Immunity: Basic Insightsmentioning

confidence: 99%

Interplay between the Hepatitis B Virus and Innate Immunity: From an Understanding to the Development of Therapeutic Concepts

Faure-Dupuy

Lucifora

Durantel

2017

Viruses

View full text Add to dashboard Cite

The hepatitis B virus (HBV) infects hepatocytes, which are the main cell type composing a human liver. However, the liver is enriched with immune cells, particularly innate cells (e.g., myeloid cells, natural killer and natural killer T-cells (NK/NKT), dendritic cells (DCs)), in resting condition. Hence, the study of the interaction between HBV and innate immune cells is instrumental to: (1) better understand the conditions of establishment and maintenance of HBV infections in this secondary lymphoid organ; (2) define the role of these innate immune cells in treatment failure and pathogenesis; and (3) design novel immune-therapeutic concepts based on the activation/restoration of innate cell functions and/or innate effectors. This review will summarize and discuss the current knowledge we have on this interplay between HBV and liver innate immunity.

show abstract

Noncanonical inflammasomes: Antimicrobial defense that does not play by the rules

Cited by 21 publications

References 74 publications

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation

Caspase‐11 non‐canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage‐mediated inflammatory responses

Interplay between the Hepatitis B Virus and Innate Immunity: From an Understanding to the Development of Therapeutic Concepts

Contact Info

Product

Resources

About