Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb:50:32-38.
doi: 10.1016/j.coi.2017.10.011. Epub 2017 Nov 10.

Recent advances in inflammasome biology

David E Place  1 , Thirumala-Devi Kanneganti  2
Affiliations
Review

Recent advances in inflammasome biology

David E Place et al. Curr Opin Immunol. 2018 Feb.

Abstract

The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Figure 2
Figure 2
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Man SM, Kanneganti T-D. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol. 2016;16:7–21. - PMC - PubMed
    1. Kesavardhana S, Kanneganti T-D. Mechanisms governing inflammasome activation, assembly and pyroptosis induction. Int Immunol. 2017 doi: 10.1093/intimm/dxx018. - DOI - PMC - PubMed
    1. Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526:666–671. - PubMed
    1. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660–665. - PubMed
    1. Janowski AM, Sutterwala FS. NLR Proteins. Humana Press; New York, NY: 2016. Atypical Inflammasomes; pp. 45–62. - PubMed

ANNOTATED REFERENCES

    1. Xing Y, Yao X, Li H, Xue G, Guo Q, Yang G, An L, Zhang Y, Meng G. Cutting Edge: TRAF6 Mediates TLR/IL-1R Signaling–Induced Nontranscriptional Priming of the NLRP3 Inflammasome. J Immunol. 2017 doi: 10.4049/jimmunol.1700175. a. This study shows how TRAF6 E3 ubiquitin ligase activity downstream of TLR/IL-1R-MyD88-IRAK signaling is required for the oligomerization of NLRP3 inflammasomes, extending our understanding of how priming occurs. - DOI - PubMed
    1. He Y, Zeng MY, Yang D, Motro B, Núñez G. Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature. 2016;530:354–357. a. One of three contemporaneous publications (Schmid-Burgk JL et al. and Shi H et al.) showing NEK7 is required for NLRP3 inflammasome activation, independent of its kinase activity. This study showed that NEK7 was required for mediating NLRP3 activation in macrophages with the CAPS-associated activating mutation NLRP3R258W. - PMC - PubMed
    1. Schmid-Burgk JL, Chauhan D, Schmidt T, Ebert TS, Reinhardt J, Endl E, Hornung V. A Genome-wide CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) Screen Identifies NEK7 as an Essential Component of NLRP3 Inflammasome Activation. J Biol Chem. 2016;291:103–109. a. One of three contemporaneous publications (He Y et al. and Shi H et al.) showing NEK7 is required for NLRP3 inflammasome activation, independent of its kinase activity. This work utilized CRISPR to identify cells resistant to NLRP3 inflammacome activation by flow cytometry. - PMC - PubMed
    1. Shi H, Wang Y, Li X, Zhan X, Tang M, Fina M, Su L, Pratt D, Bu CH, Hildebrand S, et al. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component. Nat Immunol. 2016;17:250–258. a. One of three contemporaneous publications (He Y et al. and Schmid-Burgk JL et al.) showing NEK7 is required for NLRP3 inflammasome activation, independent of its kinase activity. This work shows that the cell cycle can restrict when inflammasome activation occurs. - PMC - PubMed
    1. Zhang Z, Meszaros G, He W, Xu Y, Magliarelli H de F, Mailly L, Mihlan M, Liu Y, Gámez MP, Goginashvili A, et al. Protein kinase D at the Golgi controls NLRP3 inflammasome activation. J Exp Med. 2017 doi: 10.1084/jem.20162040. a. This study showed that PKD regulates NLRP3 inflammasome activation by phosphorylation and subsequent release from mitochondria-associated endoplasmic reticulum membranes adjacent to Golgi membranes. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources