Staphylococcus aureus activates NRLP3-dependent IL-1β secretion from human conjunctival goblet cells using α toxin and toll-like receptors 2 and 1

We used cultured human conjunctival goblet cells to determine (i) whether the toxigenic induced activation of the epithelial goblet cells requires two signals to activate the NLRP3 inflammasome, (ii) if one signal is mediated by TLR1, TLR2, or TLR6, and (iii) if the toxin α toxin is another signal f...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in cellular and infection microbiology Vol. 13; p. 1265471
Main Authors:	Li, Dayu, Hodges, Robin, AukrustNaqvi, Maria, Bair, Jeffrey, Bispo, Paulo J M, Gilmore, Michael S, Gregory-Ksander, Meredith, Dartt, Darlene A
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 27-11-2023
Subjects:	bacteria Cellular and Infection Microbiology conjunctiva goblet cells NLRP3 toll-like receptors NLRP3 bacteria goblet cells toll-like receptors conjunctiva
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	We used cultured human conjunctival goblet cells to determine (i) whether the toxigenic induced activation of the epithelial goblet cells requires two signals to activate the NLRP3 inflammasome, (ii) if one signal is mediated by TLR1, TLR2, or TLR6, and (iii) if the toxin α toxin is another signal for the activation of the inflammasome and secretion of mature IL-1β. Cultured cells were incubated with siRNA to knock down the different TLRs. After stimulation with toxigenic RN6390, pro-IL-1β synthesis, caspase-1 activity, and mature IL-1β secretion were measured. In a separate set of experiments, the cells were incubated with toxigenic RN6390 or mutant ALC837 that does not express α toxin with or without exogenous α toxin. A gentamicin protection assay was used to determine if intracellular bacteria were active. We conclude that α toxin from toxigenic triggers two separate mechanisms required for the activation of the NLRP3 inflammasome and secretion of mature IL-1β. In the first mechanism, α toxin secreted from internalized produces a pore, allowing the internalized bacteria and associated pathogen-associated molecular patterns to interact with intracellular TLR2 and, to a lesser extent, TLR1. In the second mechanism, α toxin forms a pore in the plasma membrane, leading to an efflux of cytosolic K and influx of Ca . We conclude that α toxin by these two different mechanisms triggers the synthesis of pro-IL-1β and NLRP3 components, activation of capase-1, and secretion of mature IL-1β to defend against bacterial infection.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors have contributed equally to this work Reviewed by: Zeeshan Ahmad, Wayne State University, United States; Daniel Alford Powell, University of Arizona, United States Edited by: Poonam Mudgil, Western Sydney University, Australia
ISSN:	2235-2988 2235-2988
DOI:	10.3389/fcimb.2023.1265471