Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells.
The conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3769353?pdf=render |
| _version_ | 1818945853317971968 |
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| author | Victoria E McGilligan Meredith S Gregory-Ksander Dayu Li Jonathan E Moore Robin R Hodges Michael S Gilmore Tara C B Moore Darlene A Dartt |
| author_facet | Victoria E McGilligan Meredith S Gregory-Ksander Dayu Li Jonathan E Moore Robin R Hodges Michael S Gilmore Tara C B Moore Darlene A Dartt |
| author_sort | Victoria E McGilligan |
| collection | DOAJ |
| description | The conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly expressed in wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion of biologically active IL-1β, a major initiator and promoter of inflammation. The purpose of this study was to: (1) determine whether NLRP3 is expressed in the conjunctiva and (2) determine whether goblet cells specifically contribute to innate mediated inflammation via secretion of IL-1β. We report that the receptors known to be involved in the priming and activation of the NLRP3 inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like receptor 2 are present and functional in conjunctival goblet cells. Toxin-containing Staphylococcus aureus (S. aureus), which activates the NLRP3 inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC and pro- and mature caspase 1 in conjunctival goblet cells. The biologically active form of IL-1β was detected in goblet cell culture supernatants in response to S. aureus, which was reduced when the cells were treated with the caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be activated in conjunctival goblet cells by toxin-containing S. aureus via the caspase 1 pathway to secrete mature IL1-β. Thus goblet cells contribute to the innate immune response in the conjunctiva by activation of the NLRP3 inflammasome. |
| first_indexed | 2024-12-20T08:05:43Z |
| format | Article |
| id | doaj.art-86c2d0c103c24a71bed12027865fe906 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:05:43Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-86c2d0c103c24a71bed12027865fe9062022-12-21T19:47:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7401010.1371/journal.pone.0074010Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells.Victoria E McGilliganMeredith S Gregory-KsanderDayu LiJonathan E MooreRobin R HodgesMichael S GilmoreTara C B MooreDarlene A DarttThe conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly expressed in wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion of biologically active IL-1β, a major initiator and promoter of inflammation. The purpose of this study was to: (1) determine whether NLRP3 is expressed in the conjunctiva and (2) determine whether goblet cells specifically contribute to innate mediated inflammation via secretion of IL-1β. We report that the receptors known to be involved in the priming and activation of the NLRP3 inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like receptor 2 are present and functional in conjunctival goblet cells. Toxin-containing Staphylococcus aureus (S. aureus), which activates the NLRP3 inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC and pro- and mature caspase 1 in conjunctival goblet cells. The biologically active form of IL-1β was detected in goblet cell culture supernatants in response to S. aureus, which was reduced when the cells were treated with the caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be activated in conjunctival goblet cells by toxin-containing S. aureus via the caspase 1 pathway to secrete mature IL1-β. Thus goblet cells contribute to the innate immune response in the conjunctiva by activation of the NLRP3 inflammasome.http://europepmc.org/articles/PMC3769353?pdf=render |
| spellingShingle | Victoria E McGilligan Meredith S Gregory-Ksander Dayu Li Jonathan E Moore Robin R Hodges Michael S Gilmore Tara C B Moore Darlene A Dartt Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. PLoS ONE |
| title | Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. |
| title_full | Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. |
| title_fullStr | Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. |
| title_full_unstemmed | Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. |
| title_short | Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells. |
| title_sort | staphylococcus aureus activates the nlrp3 inflammasome in human and rat conjunctival goblet cells |
| url | http://europepmc.org/articles/PMC3769353?pdf=render |
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