The inflammasome: firing up innate immunity

Kanneganti, Thirumala‐Devi

doi:10.1111/imr.12297

Cited by 64 publications

(43 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since its initial characterization approximately 13 years ago (Martinon et al , 2002), the study of the inflammasome has quickly become a burgeoning field (Kanneganti, 2015). During this time, impressive advances have been made in understanding the molecular mechanisms of how the inflammasome senses pathogens and danger signals to drive inflammatory outputs.…”

Section: Discussionmentioning

confidence: 99%

“…The inflammasome surveys the cytosol for signals of intracellular pathogens or host cell damage. Canonical inflammasome activation begins with the detection of a cytosolic ligand or danger signal, which induces the selfoligomerization of a corresponding inflammasome sensor (Martinon et al, 2009), typically either nucleotide-binding domain, leucine-rich repeat containing receptors (NLRs) or AIM2-like receptors (Kanneganti, 2015). Following receptor oligomerization, the adaptor protein apoptosisassociated speck-like protein with a caspase recruitment domain (ASC) is recruited to the activated sensor.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish

Vincent

Freisinger

Lam

et al. 2015

Cellular Microbiology

View full text Add to dashboard Cite

Summary The inflammasome is an innate immune complex whose rapid inflammatory outputs play a critical role in controlling infection, however the host cells that mediate inflammasome responses in vivo are not well defined. Using zebrafish larvae, we examined the cellular immune responses to inflammasome activation during infection. We compared the host responses to two Listeria monocytogenes strains: wild type and Lm-pyro, a strain engineered to activate the inflammasome via ectopic expression of flagellin. Infection with Lm-pyro led to activation of the inflammasome, macrophage pyroptosis, and ultimately attenuation of virulence. Depletion of caspase A, the zebrafish caspase-1 homolog, restored Lm-pyro virulence. Inflammasome activation specifically recruited macrophages to infection sites, whereas neutrophils were equally recruited to WT and Lm-pyro infections. Similar to caspase A depletion, macrophage deficiency rescued Lm-pyro virulence to wild type levels, while defective neutrophils had no specific effect. Neutrophils were however important for general clearance of L. monocytogenes, as both wild type and Lm-pyro were more virulent in larvae with defective neutrophils. This study characterizes a novel model for inflammasome studies in an intact host, establishes the importance of macrophages during inflammasome responses, and adds importance to the role of neutrophils in controlling L. monocytogenes infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish

Vincent

Freisinger

Lam

et al. 2015

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…Several distinct inflammasomes have been identified accordingly to the unique sensor molecule responsible for detecting a specific trigger (PAMPs or DAMPs). These intracellular receptors belong to the nucleotide-binding domain leucine-rich repeat containing (NLR) protein family or to AIM2-like receptor (ALR) members [114,115] . These proteins have an N-terminal pyrin domain (PYD) in common, required for homotypic interaction with the PYD domain of the bipartite adaptor ASC, which contains a CARD domain essential for the recruitment of inactive caspases [116] .…”

Section: Inflammasomes and The Activation Of Innate Immunitymentioning

confidence: 99%

Cellular Innate Immunity: An Old Game with New Players

et al. 2016

View full text Add to dashboard Cite

Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.

show abstract

“…The difference in infection and disease pathogenesis between the mouse strains arises from hypofunctional activity of NAIP5 within the Lgn1 locus on mouse chromosome 13 of A mice [3,[61][62][63][64][65]. NAIP5 is a member of the NAIP family of NLR proteins that heterodimerize with NLRC4 to generate the NLRC4 inflammasome that is involved in the recognition of bacterial flagellin and components of bacterial type III secretion systems [66][67][68][69][70]. To achieve permissive L. pneumophila infection in normally restrictive mouse strains, researchers often use an aflagellated mutant strain of L. pneumophila that bypasses stimulation of the NLRC4 inflammasome, as well as TLR5, and permits replication of the bacteria in vivo [71][72][73].…”

Section: The Immune Response To L Pneumophila In Micementioning

confidence: 99%

The regulation of acute immune responses to the bacterial lung pathogenLegionella pneumophila

Brown

Yang

Hartland

et al. 2016

Journal of Leukocyte Biology

View full text Add to dashboard Cite

causes Legionnaires' disease, a severe and potentially fatal bacterial pneumonia in immunocompromised individuals. Despite the understanding that a robust inflammatory response is important for control of infection, our understanding of the network of molecular and cellular events within the lung that function to clear the bacterium is not clearly understood. This review compiles our understanding of the various molecular and cellular pathways stimulated upon infection with and considers recently published advances that focus on the immune response to in the lungs of mice. This includes a cooperative network of tissue-resident and inflammatory phagocytes, including alveolar macrophages (AM)s, neutrophils, and inflammatory monocytes/monocyte-derived cells (MC) that contribute to the acute inflammatory response and restrict the bacteria via distinct intracellular pathways. The understanding of this difference in cellular activity in response to infection provides insight into the innate immune responses within the tissues in general and may prompt novel means of clinical management of bacterial infections in an era of increasing emergence of antibiotic resistance.

show abstract

The inflammasome: firing up innate immunity

Cited by 64 publications

References 24 publications

Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish

Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish

Cellular Innate Immunity: An Old Game with New Players

The regulation of acute immune responses to the bacterial lung pathogenLegionella pneumophila

Contact Info

Product

Resources

About