Sumpf, Kristina

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.journal","Experimental Parasitology"],["dc.bibliographiccitation.lastpage","54"],["dc.bibliographiccitation.volume","180"],["dc.contributor.author","Sumpf, Kristina"],["dc.contributor.author","Nast, Roswitha"],["dc.contributor.author","Downie, Bryan R."],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Lüder, Carsten G. K."],["dc.date.accessioned","2019-08-07T07:23:22Z"],["dc.date.available","2019-08-07T07:23:22Z"],["dc.date.issued","2017"],["dc.description.abstract","Toxoplasma gondii is a ubiquitous apicomplexan parasite of mammals and birds and an important pathogen of humans. IFN-γ is the major mediator of host resistance against T. gondii but intriguingly, parasite-infected host cells including macrophages are severely impaired to respond to IFN-γ due to defective transcriptional activation of target genes. Here, we tested the possibility that the impaired responsiveness of T. gondii-infected macrophages to IFN-γ can be restored by inhibiting histone deacetylases (HDACs) using the class I-specific inhibitor MS-275. Treatment of RAW264.7 cells with MS-275 indeed increased MHC class II surface expression in infected and non-infected cells and largely abolished the inhibition of IFN-γ-regulated MHC class II expression exerted by T. gondii. Genome-wide transcriptome profiling revealed that MS-275 increased mean mRNA levels of IFN-γ-regulated genes particularly in non-infected macrophages. Transcript levels of 33% of IFN-γ secondary response genes but only those of a few primary response genes were also increased by MS-275 in T. gondii-infected cells. Importantly, the unresponsiveness of parasite-infected cells to IFN-γ was however not abolished by MS-275. Furthermore, MS-275 also up-regulated several anti-inflammatory cytokines or signaling molecules in T. gondii-infected macrophages. It additionally regulated expression of more than 2500 genes in non-infected macrophages expression of which was surprisingly counteracted by prior infection with T. gondii. FACS analysis and immunofluorescence microscopy revealed that MS-275 did not considerably diminish the number of parasite-positive cells or the intracellular replication in macrophages stimulated or not with IFN-γ. Thus, a supportive therapy using MS-275 appears inappropriate for treatment of toxoplasmosis."],["dc.identifier.doi","10.1016/j.exppara.2017.02.011"],["dc.identifier.pmid","28189488"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62330"],["dc.language.iso","en"],["dc.relation.eissn","1090-2449"],["dc.relation.issn","0014-4894"],["dc.title","Histone deacetylase inhibitor MS-275 augments expression of a subset of IFN-γ-regulated genes in Toxoplasma gondii-infected macrophages but does not improve parasite control"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","456"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Trends in Parasitology"],["dc.bibliographiccitation.lastpage","459"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Lueder, Carsten Guenter Kurt"],["dc.contributor.author","Sumpf, Kristina"],["dc.contributor.author","Nast, Roswitha"],["dc.date.accessioned","2018-11-07T09:50:52Z"],["dc.date.available","2018-11-07T09:50:52Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1016/j.pt.2015.08.006"],["dc.identifier.isi","000363077200003"],["dc.identifier.pmid","26422772"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35795"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Sci Ltd"],["dc.relation.issn","1471-5007"],["dc.relation.issn","1471-4922"],["dc.title","Releasing the Brake on IFN-gamma Signaling on Infection"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]