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
. 2009 Feb;21(1):10-6.
doi: 10.1016/j.coi.2009.01.006. Epub 2009 Feb 14.

Sensing pathogens and danger signals by the inflammasome

Joao H F Pedra  1 , Suzanne L Cassel, Fayyaz S Sutterwala
Affiliations
Review

Sensing pathogens and danger signals by the inflammasome

Joao H F Pedra et al. Curr Opin Immunol. 2009 Feb.

Abstract

The NLR (nucleotide-binding domain leucine-rich repeat containing) family of intracellular sensors is a crucial component of the innate immune system. A number of NLR family members can form multiprotein complexes, called inflammasomes, and are capable of activating the cysteine protease caspase-1 in response to a wide range of stimuli including both microbial and self-molecules. Caspase-1 activation leads to processing and secretion of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-18, which play crucial roles in host defense to infectious insults. Dysregulation of the inflammasome has also been linked to a number of autoinflammatory and autoimmune disorders. Recent advances in the inflammasome field will be discussed in this review.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Inflammasome activation by microbes and danger signals. Several NLRs can form multiprotein complexes called inflammasomes. Activation of the inflammasome results in activation of the cysteine protease caspase-1 and the resultant processing of pro-IL-1β, pro-IL-18 and pro-IL-33 into biologically active IL-1β, IL-18 and IL-33 respectively. Activation of the NLRC4 inflammasome following infection of macrophages with S. typhimurium, P. aeruginosa, S. flexneri or L. pneumophila requires a functional type III or type IV secretion system. Bacterial-derived cytosolic flagellin augments caspase-1 activation following infection with L. pneumophila, S. typhimurium, and P. aeruginosa possibly through a Naip5-dependent pathway. Anthrax lethal toxin and MDP are capable of activating the NLRP1 inflammasome in a manner that may also require NOD2. A wide variety of stimuli including bacterial pore-forming toxins, ATP, DNA, bacterial RNA and crystals such as silica, asbestos, uric acid, alum and amyloid-β can activate the NLRP3 inflammasome. NLRP3 activating PAMPs and DAMPs induce a K+ efflux and the generation of mitochondrial-derived ROS that play a role in NLRP3 inflammasome activation by an unknown mechanism. Crystal induced lysosomal damage, and the resultant release of cathepsin B, are also postulated to play a role in NLRP3 inflammasome activation by an unknown mechanism.
See this image and copyright information in PMC

Comment in

  • Innate resistance and inflammation.
    Gordon S, Trinchieri G. Gordon S, et al. Curr Opin Immunol. 2009 Feb;21(1):1-2. doi: 10.1016/j.coi.2009.02.001. Epub 2009 Feb 14. Curr Opin Immunol. 2009. PMID: 19223161 No abstract available.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–190. - PubMed
    1. Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8:279–289. - PMC - PubMed
    1. Ye Z, Ting JP. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr Opin Immunol. 2008;20:3–9. - PubMed
    1. Dostert C, Meylan E, Tschopp J. Intracellular pattern-recognition receptors. Adv Drug Deliv Rev. 2008;60:830–840. - PubMed
    1. Mariathasan S, Monack DM. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol. 2007;7:31–40. - PubMed

Publication types

MeSH terms