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dc.contributor.authorHarvey, R.-
dc.contributor.authorHughes, C.-
dc.contributor.authorPaton, A.-
dc.contributor.authorTrappetti, C.-
dc.contributor.authorPaton, J.-
dc.contributor.authorTweten, R.-
dc.contributor.editorNeyrolles, O.-
dc.identifier.citationPLoS One, 2014; 9(8):e103625-1-e103625-9-
dc.description.abstractStreptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism.-
dc.description.statementofresponsibilityMansour Ebrahimi, Parisa Aghagolzadeh, Narges Shamabadi, Ahmad Tahmasebi, Mohammed Alsharifi, David L. Adelson, Farhid Hemmatzadeh, Esmaeil Ebrahimie-
dc.rights© 2014 Harvey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.-
dc.subjectCells, Cultured-
dc.subjectStreptococcus pneumoniae-
dc.subjectBacterial Proteins-
dc.subjectGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subjectDNA Primers-
dc.subjectBlotting, Western-
dc.subjectEnzyme-Linked Immunosorbent Assay-
dc.subjectAnalysis of Variance-
dc.subjectPolymerase Chain Reaction-
dc.subjectSequence Analysis, DNA-
dc.subjectSpecies Specificity-
dc.titleThe impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent-
dc.typeJournal article-
dc.identifier.orcidTrappetti, C. [0000-0001-8272-0068]-
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]-
Appears in Collections:Aurora harvest 3
Molecular and Biomedical Science publications

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