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
. 2022 May 12:13:896353.
doi: 10.3389/fimmu.2022.896353. eCollection 2022.

Activation and Regulation of NLRP3 by Sterile and Infectious Insults

Srijon K Banerjee  1 , Ayan Chatterjee  2 , Shamba Gupta  3 , Abhinit Nagar  4
Affiliations
Review

Activation and Regulation of NLRP3 by Sterile and Infectious Insults

Srijon K Banerjee et al. Front Immunol. .

Abstract

Nod-Like Receptor (NLR) is the largest family of Pathogen Recognition Receptors (PRRs) that patrols the cytosolic environment. NLR engagement drives caspase-1 activation that cleaves pro-IL-1B which then gets secreted. Released IL-1B recruits immune cells to the site of infection/injury. Caspase-1 also cleaves Gasdermin-D (GSDM-D) that forms pores within the plasma membrane driving inflammatory cell death called pyroptosis. NLRP3 is the most extensively studied NLR. The NLRP3 gene is encoded by 9 exons, where exon 1 codes for pyrin domain, exon 3 codes for NACHT domain, and Leucine Rich Repeat (LRR) domain is coded by exon 4-9. Exon 2 codes for a highly disorganized loop that connects the rest of the protein to the pyrin domain and may be involved in NLRP3 regulation. The NLRP3 inflammasome is activated by many structurally divergent agonists of microbial, environmental, and host origin. Activated NLRP3 interacts with an adaptor protein, ASC, that bridges it to pro-Caspase-1 forming a multi-protein complex called inflammasome. Dysregulation of NLRP3 inflammasome activity is a hallmark of pathogenesis in several human diseases, indicating its highly significant clinical relevance. In this review, we summarize the existing knowledge about the mechanism of activation of NLRP3 and its regulation during activation by infectious and sterile triggers.

Keywords: Inflammasome; Microbes; NLRP3; Sterile Inflammation; extracellular vesicles; post-translational modification.

PubMed Disclaimer

Conflict of interest statement

Author AN was employed by Luminex Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Two-step mechanism of NLRP3 activation. (A) TLR/IL1-R engagement leads to NF-κB activation driving transcriptional upregulation of inflammasome components (Signal 1). NLRP3 is then activated upon sensing unknown direct agonists (Signal 2), which can be (B) infectious, (C) sterile and can also be mediated through (D) exosomes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Evavold CL, Kagan JC. Inflammasomes: Threat-Assessment Organelles of the Innate Immune System. Immunity (2019) 51(4):609–24. doi: 10.1016/j.immuni.2019.08.005 - DOI - PMC - PubMed
    1. Dinarello CA. The IL-1 Family and Inflammatory Diseases. Clin Exp Rheumatol (2002) 20(5 Suppl 27):S1–13. - PubMed
    1. Dinarello CA. Infection, Fever, and Exogenous and Endogenous Pyrogens: Some Concepts Have Changed. J Endotoxin Res (2004) 10(4):201–22. doi: 10.1179/096805104225006129 - DOI - PubMed
    1. Dinarello CA. Immunological and Inflammatory Functions of the Interleukin-1 Family. Annu Rev Immunol (2009) 27:519–50. doi: 10.1146/annurev.immunol.021908.132612 - DOI - PubMed
    1. Dinarello CA. IL-1: Discoveries, Controversies and Future Directions. Eur J Immunol (2010) 40(3):599–606. doi: 10.1002/eji.201040319 - DOI - PubMed