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dc.contributor.authorLi, Dayuen_US
dc.contributor.authorHodges, Robin Ren_US
dc.contributor.authorBispo, Pauloen_US
dc.contributor.authorGilmore, Michael Sen_US
dc.contributor.authorGregory-Ksander, Meredithen_US
dc.contributor.authorDartt, Darlene Aen_US
dc.date.accessioned2018-02-26T20:41:02Z
dc.date.issued2016en_US
dc.identifier.citationLi, Dayu, Robin R Hodges, Paulo Bispo, Michael S Gilmore, Meredith Gregory-Ksander, and Darlene A Dartt. 2016. “Neither non-toxigenic Staphylococcus aureus nor commensal S. epidermidi activates NLRP3 inflammasomes in human conjunctival goblet cells.” BMJ Open Ophthalmology 2 (1): e000101. doi:10.1136/bmjophth-2017-000101. http://dx.doi.org/10.1136/bmjophth-2017-000101.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34868877
dc.description.abstractPurpose The conjunctiva is a wet mucosal surface surrounding the cornea that is continuously exposed to pathogens. Nevertheless, persistent inflammation is not observed. We examined if the NOD-like receptor pyrin domain 3 (NLRP3) inflammasome functions as a sensor that distinguishes commensal and non-pathogenic bacteria from pathogenic bacteria in human conjunctival goblet cells. Methods: Goblet cells were grown from human conjunctiva and co-cultured with commensal Staphylococcus epidermidis, isogenic non-toxigenic S. aureus ACL135 and as a control toxigenic S. aureus RN6390. Activation of the NLRP3 inflammasome was determined by measuring changes in NF-κB activity, expression of pro-interleukin (IL)-1β and NLRP3, activation of caspase-1 and secretion of mature IL-1β. Goblet cell mucin secretion was measured in parallel. Results: While all three strains of bacteria were able to bind to goblet cells, neither commensal S. epidermidis nor isogenic non-toxigenic S. aureus ACL135 was able to stimulate an increase in (1) NF-κB activity, (2) pro-IL-1β and NLRP3 expression, (3) caspase-1 activation, (4) mature IL-1β and (5) mucin secretion. Toxigenic S. aureus, the positive control, increased these values: knockdown of NLRP3 with small interfering RNA (siRNA) completely abolished the toxigenic S. aureus-induced expression of pro-IL-1β and secretion of mature IL-1β. Conclusions: We conclude that NLRP3 serves as a sensor capable of discriminating commensal and non-pathogenic bacteria from pathogenic bacteria in conjunctival goblet cells, and that activation of the NLRP3 inflammasome induced by pathogenic bacteria mediates secretion of both mature IL-1β and large secretory mucins from these cells.en
dc.language.isoen_USen
dc.publisherBMJ Publishing Groupen
dc.relation.isversionofdoi:10.1136/bmjophth-2017-000101en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751869/pdf/en
dash.licenseLAAen_US
dc.subjectinflammationen
dc.subjectinfectionen
dc.titleNeither non-toxigenic Staphylococcus aureus nor commensal S. epidermidi activates NLRP3 inflammasomes in human conjunctival goblet cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMJ Open Ophthalmologyen
dash.depositing.authorHodges, Robin Ren_US
dc.date.available2018-02-26T20:41:02Z
dc.identifier.doi10.1136/bmjophth-2017-000101*
dash.contributor.affiliatedBispo, Paulo
dash.contributor.affiliatedHodges, Robin
dash.contributor.affiliatedDartt, Darlene
dash.contributor.affiliatedGregory-Ksander, Meredith
dash.contributor.affiliatedGilmore, Michael


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