Activation and Regulation of NLRP3 by Sterile and Infectious Insults
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 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.896353/full |
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| author | Srijon K. Banerjee Ayan Chatterjee Shamba Gupta Abhinit Nagar |
| author_facet | Srijon K. Banerjee Ayan Chatterjee Shamba Gupta Abhinit Nagar |
| author_sort | Srijon K. Banerjee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T16:24:07Z |
| format | Article |
| id | doaj.art-8ae1e1be2ebe4124989e9e436268a46b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T16:24:07Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8ae1e1be2ebe4124989e9e436268a46b2022-12-22T00:18:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.896353896353Activation and Regulation of NLRP3 by Sterile and Infectious InsultsSrijon K. Banerjee0Ayan Chatterjee1Shamba Gupta2Abhinit Nagar3Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United StatesDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, NY, United StatesFlow Cytometry, Luminex Corporation, Austin, TX, United StatesNod-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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.896353/fullNLRP3InflammasomeMicrobesSterile Inflammationextracellular vesiclespost-translational modification |
| spellingShingle | Srijon K. Banerjee Ayan Chatterjee Shamba Gupta Abhinit Nagar Activation and Regulation of NLRP3 by Sterile and Infectious Insults Frontiers in Immunology NLRP3 Inflammasome Microbes Sterile Inflammation extracellular vesicles post-translational modification |
| title | Activation and Regulation of NLRP3 by Sterile and Infectious Insults |
| title_full | Activation and Regulation of NLRP3 by Sterile and Infectious Insults |
| title_fullStr | Activation and Regulation of NLRP3 by Sterile and Infectious Insults |
| title_full_unstemmed | Activation and Regulation of NLRP3 by Sterile and Infectious Insults |
| title_short | Activation and Regulation of NLRP3 by Sterile and Infectious Insults |
| title_sort | activation and regulation of nlrp3 by sterile and infectious insults |
| topic | NLRP3 Inflammasome Microbes Sterile Inflammation extracellular vesicles post-translational modification |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.896353/full |
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