Neisseria gonorrhoeae Activates the Proteinase Cathepsin B to Mediate the Signaling Activities of the NLRP3 and ASC-Containing Inflammasome Article Swipe
Joseph A. Duncan
,
Xi Gao
,
Max Tze Han Huang
,
Brian P. O’Connor
,
Christopher Thomas
,
Stephen B. Willingham
,
Dan T. Bergstralh
,
Gary A. Jarvis
,
P. Frederick Sparling
,
Jenny P.‐Y. Ting
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/0w96-mw14
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/0w96-mw14
Neisseria gonorrhoeae is a common sexually transmitted pathogen that significantly impacts female fertility, neonatal health, and transmission of HIV worldwide. N. gonorrhoeae usually causes localized inflammation of the urethra and cervix by inducing production of IL-1β and other inflammatory cytokines. Several NLR (Nucleotide binding domain, Leucine Rich Repeat) proteins are implicated in the formation of pro-IL-1β-processing complexes called inflammasomes in response to pathogens. We demonstrate that NLRP3 (cryopyrin,NALP3) is the primary NLR required for IL-1β/IL-18 secretion in response to N. gonorrhoeae in monocytes. We also show that N. gonorrhoeae infection promotes NLRP3-dependent monocytic cell death via pyronecrosis, a recently described pathway with morphological features of necrosis, including release of the strong inflammatory mediator HMBG1. Additionally, N. gonorrhoeae activates the cysteine protease Cathepsin-B as measured by the breakdown of a Cathepsin B substrate. Inhibition of Cathepsin B shows that this protease is an apical controlling step in the downstream activities of NLRP3 including IL-1β production, pyronecrosis, and HMGB1 release. Non-pathogenic Neisseria strains (N. cinerea and N. flavescens) do not activate NLRP3 as robustly as N. gonorrhoeae. Conditioned media from N. gonorrhoeae contains factors capable of initiating the NLRP3 mediated signaling events. Isolated N. gonorrhoeae lipooligosaccharide, a known virulence factor from this bacterium that is elaborated from the bacterium in the form of outer membrane blebs, activates both NLRP3-induced IL-1β secretion and pyronecrosis. Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N. gonorrhoeae.
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- Type
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- Language
- en
- Landing Page
- https://doi.org/10.17615/0w96-mw14
- OA Status
- green
- Cited By
- 22
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4298359959Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.17615/0w96-mw14Digital Object Identifier
- Title
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Neisseria gonorrhoeae Activates the Proteinase Cathepsin B to Mediate the Signaling Activities of the NLRP3 and ASC-Containing InflammasomeWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2020Year of publication
- Publication date
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2020-11-09Full publication date if available
- Authors
-
Joseph A. Duncan, Xi Gao, Max Tze Han Huang, Brian P. O’Connor, Christopher Thomas, Stephen B. Willingham, Dan T. Bergstralh, Gary A. Jarvis, P. Frederick Sparling, Jenny P.‐Y. TingList of authors in order
- Landing page
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https://doi.org/10.17615/0w96-mw14Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.17615/0w96-mw14Direct OA link when available
- Concepts
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Neisseria gonorrhoeae, Inflammasome, Microbiology, Cathepsin B, Chemistry, Biology, Enzyme, Biochemistry, ReceptorTop concepts (fields/topics) attached by OpenAlex
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22Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2022: 3, 2020: 2, 2019: 1, 2018: 2Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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