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Molecular mechanisms activating the NAIP‐NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer

Kay, Callum; Wang, Runli; Kirkby, Max; Man, Si Ming

Description

Cytosolic innate immune sensing is a cornerstone of innate immunity in mammalian cells and provides a surveillance system for invading pathogens and endogenous danger signals. The NAIP‐NLRC4 inflammasome responds to cytosolic flagellin, and the inner rod and needle proteins of the type 3 secretion system of bacteria. This complex induces caspase‐1‐dependent proteolytic cleavage of the proinflammatory cytokines IL‐1β and IL‐18, and the pore‐forming protein gasdermin D, leading to inflammation...[Show more]

dc.contributor.authorKay, Callum
dc.contributor.authorWang, Runli
dc.contributor.authorKirkby, Max
dc.contributor.authorMan, Si Ming
dc.date.accessioned2021-01-19T03:08:23Z
dc.identifier.issn0105-2896
dc.identifier.urihttp://hdl.handle.net/1885/219783
dc.description.abstractCytosolic innate immune sensing is a cornerstone of innate immunity in mammalian cells and provides a surveillance system for invading pathogens and endogenous danger signals. The NAIP‐NLRC4 inflammasome responds to cytosolic flagellin, and the inner rod and needle proteins of the type 3 secretion system of bacteria. This complex induces caspase‐1‐dependent proteolytic cleavage of the proinflammatory cytokines IL‐1β and IL‐18, and the pore‐forming protein gasdermin D, leading to inflammation and pyroptosis, respectively. Localized responses triggered by the NAIP‐NLRC4 inflammasome are largely protective against bacterial pathogens, owing to several mechanisms, including the release of inflammatory mediators, liberation of concealed intracellular pathogens for killing by other immune mechanisms, activation of apoptotic caspases, caspase‐7, and caspase‐8, and expulsion of an entire infected cell from the mammalian host. In contrast, aberrant activation of the NAIP‐NLRC4 inflammasome caused by de novo gain‐of‐function mutations in the gene encoding NLRC4 can lead to macrophage activation syndrome, neonatal enterocolitis, fetal thrombotic vasculopathy, familial cold autoinflammatory syndrome, and even death. Some of these clinical manifestations could be treated by therapeutics targeting inflammasome‐associated cytokines. In addition, the NAIP‐NLRC4 inflammasome has been implicated in the pathogenesis of colorectal cancer, melanoma, glioma, and breast cancer. However, no consensus has been reached on its function in the development of any cancer types. In this review, we highlight the latest advances in the activation mechanisms and structural assembly of the NAIP‐NLRC4 inflammasome, and the functions of this inflammasome in different cell types. We also describe progress toward understanding the role of the NAIP‐NLRC4 inflammasome in infectious diseases, autoinflammatory diseases, and cancer.
dc.description.sponsorshipAustralian National University; National Health and Medical Research Council, Grant/Award Number: APP1141504,, APP1146864, APP1162103 and APP1163358; R.D. Wright Career Development Fellowship, Grant/Award Number: APP1162025
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherMunksgaard International Publishers
dc.rights© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
dc.sourceImmunological Reviews
dc.subjectassembly
dc.subjectautoimmunity
dc.subjectcell death
dc.subjectepithelial cells
dc.subjectexpulsion
dc.subjectgasdermin
dc.subjectHelicobacter pylori
dc.subjectinflammatory caspases
dc.subjectLegionella pneumophila
dc.subjectnecrosis
dc.subjectneutrophils
dc.subjectpattern-recognition receptors
dc.subjectphosphorylation
dc.subjectPseudomonas aeruginosa
dc.subjectSalmonella Typhimurium
dc.subjectstructure
dc.titleMolecular mechanisms activating the NAIP‐NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume297
dc.date.issued2020
local.identifier.absfor110707 - Innate Immunity
local.identifier.ariespublicationu1036742xPUB54
local.publisher.urlhttps://www.wiley.com/en-gb
local.type.statusAccepted Version
local.contributor.affiliationKay, Callum, College of Health and Medicine, ANU
local.contributor.affiliationWang, Runli (Jerry), College of Health and Medicine, ANU
local.contributor.affiliationKirkby, Max, College of Health and Medicine, ANU
local.contributor.affiliationMan, Si Ming, College of Health and Medicine, ANU
local.description.embargo2021-07-29
dc.relationhttp://purl.org/au-research/grants/nhmrc/1141504
dc.relationhttp://purl.org/au-research/grants/nhmrc/1146864
local.bibliographicCitation.startpage67
local.bibliographicCitation.lastpage82
local.identifier.doi10.1111/imr.12906
local.identifier.absseo920108 - Immune System and Allergy
dc.date.updated2020-11-02T04:19:35Z
dcterms.accessRightsOpen Access
dc.provenancehttps://v2.sherpa.ac.uk/id/publication/2497..."The Accepted Version can be archived in a Non-Commercial Institutional Repository. 12 months embargo" from SHERPA/RoMEO site (as at 5/02/2021). This is the peer reviewed version of the following article: [Kay, Callum, et al. "Molecular mechanisms activating the NAIP‐NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer." Immunological Reviews 297.1 (2020): 67-82.], which has been published in final form at https://dx.doi.org/10.1111/imr.12906. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions
CollectionsANU Research Publications

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