Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells.
Apoptosis
Caspase-1
Caspase-3/7
Cell death
IL-1β
NLRP3 inflammasome
Pyroptosis
Streptococcus pneumoniae
Journal
Journal of innate immunity
ISSN: 1662-8128
Titre abrégé: J Innate Immun
Pays: Switzerland
ID NLM: 101469471
Informations de publication
Date de publication:
2022
2022
Historique:
received:
21
01
2021
accepted:
14
06
2021
pubmed:
14
9
2021
medline:
6
5
2022
entrez:
13
9
2021
Statut:
ppublish
Résumé
Epithelial cells play a crucial role in detection of the pathogens as well as in initiation of the host immune response. Streptococcus pneumoniae (pneumococcus) is a typical colonizer of the human nasopharynx, which can disseminate to the lower respiratory tract and subsequently cause severe invasive diseases such as pneumonia, sepsis, and meningitis. Hydrogen peroxide (H2O2) is produced by pneumococci as a product of the pyruvate oxidase SpxB. However, its role as a virulence determinant in pneumococcal infections of the lower respiratory tract is not well understood. In this study, we investigated the role of pneumococcal-derived H2O2 in initiating epithelial cell death by analyzing the interplay between 2 key cell death pathways, namely, apoptosis and pyroptosis. We demonstrate that H2O2 primes as well as activates the NLRP3 inflammasome and thereby mediates IL-1β production and release. Furthermore, we show that pneumococcal H2O2 causes cell death via the activation of both apoptotic as well as pyroptotic pathways which are mediated by the activation of caspase-3/7 and caspase-1, respectively. However, H2O2-mediated IL-1β release itself occurs mainly via apoptosis.
Identifiants
pubmed: 34515145
pii: 000517855
doi: 10.1159/000517855
pmc: PMC9149442
doi:
Substances chimiques
Inflammasomes
0
Interleukin-1beta
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Hydrogen Peroxide
BBX060AN9V
Caspase 1
EC 3.4.22.36
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
192-206Informations de copyright
© 2021 The Author(s) Published by S. Karger AG, Basel.
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