Swierzy, Izabela J.

[["dc.bibliographiccitation.journal","Frontiers in Cellular and Infection Microbiology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Rahman, Md. Taibur"],["dc.contributor.author","Swierzy, Izabela J."],["dc.contributor.author","Downie, Bryan"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Blume, Martin"],["dc.contributor.author","McConville, Malcolm J."],["dc.contributor.author","Lüder, Carsten G. K."],["dc.date.accessioned","2022-01-11T14:06:06Z"],["dc.date.available","2022-01-11T14:06:06Z"],["dc.date.issued","2021"],["dc.description.abstract","Toxoplasma gondii is an obligatory intracellular parasite that causes persistent infections in birds and mammals including ~30% of the world’s human population. Differentiation from proliferative and metabolically active tachyzoites to largely dormant bradyzoites initiates the chronic phase of infection and occurs predominantly in brain and muscle tissues. Here we used murine skeletal muscle cells (SkMCs) to decipher host cellular factors that favor T. gondii bradyzoite formation in terminally differentiated and syncytial myotubes, but not in proliferating myoblast precursors. Genome-wide transcriptome analyses of T. gondii -infected SkMCs and non-infected controls identified ~6,500 genes which were differentially expressed (DEGs) in myotubes compared to myoblasts, largely irrespective of infection. On the other hand, genes related to central carbohydrate metabolism, to redox homeostasis, and to the Nrf2-dependent stress response pathway were enriched in both infected myoblast precursors and myotubes. Stable isotope-resolved metabolite profiling indicated increased fluxes into the oxidative branch of the pentose phosphate pathway (OxPPP) in infected myoblasts and into the TCA cycle in infected myotubes. High OxPPP activity in infected myoblasts was associated with increased NADPH/NADP + ratio while myotubes exhibited higher ROS levels and lower expression of anti-oxidants and detoxification enzymes. Pharmacological reduction of ROS levels in SkMCs inhibited bradyzoite differentiation, while increased ROS induced bradyzoite formation. Thus, we identified a novel host cell-dependent mechanism that triggers stage conversion of T. gondii into persistent tissue cysts in its natural host cell type."],["dc.description.abstract","Toxoplasma gondii is an obligatory intracellular parasite that causes persistent infections in birds and mammals including ~30% of the world’s human population. Differentiation from proliferative and metabolically active tachyzoites to largely dormant bradyzoites initiates the chronic phase of infection and occurs predominantly in brain and muscle tissues. Here we used murine skeletal muscle cells (SkMCs) to decipher host cellular factors that favor T. gondii bradyzoite formation in terminally differentiated and syncytial myotubes, but not in proliferating myoblast precursors. Genome-wide transcriptome analyses of T. gondii -infected SkMCs and non-infected controls identified ~6,500 genes which were differentially expressed (DEGs) in myotubes compared to myoblasts, largely irrespective of infection. On the other hand, genes related to central carbohydrate metabolism, to redox homeostasis, and to the Nrf2-dependent stress response pathway were enriched in both infected myoblast precursors and myotubes. Stable isotope-resolved metabolite profiling indicated increased fluxes into the oxidative branch of the pentose phosphate pathway (OxPPP) in infected myoblasts and into the TCA cycle in infected myotubes. High OxPPP activity in infected myoblasts was associated with increased NADPH/NADP + ratio while myotubes exhibited higher ROS levels and lower expression of anti-oxidants and detoxification enzymes. Pharmacological reduction of ROS levels in SkMCs inhibited bradyzoite differentiation, while increased ROS induced bradyzoite formation. Thus, we identified a novel host cell-dependent mechanism that triggers stage conversion of T. gondii into persistent tissue cysts in its natural host cell type."],["dc.identifier.doi","10.3389/fcimb.2021.798549"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97828"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2235-2988"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","The Redox Homeostasis of Skeletal Muscle Cells Regulates Stage Differentiation of Toxoplasma gondii"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","7229"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Swierzy, Izabela J."],["dc.contributor.author","Händel, Ulrike"],["dc.contributor.author","Kaever, Alexander"],["dc.contributor.author","Jarek, Michael"],["dc.contributor.author","Scharfe, Maren"],["dc.contributor.author","Schlüter, Dirk"],["dc.contributor.author","Lüder, Carsten G. K."],["dc.date.accessioned","2019-07-09T11:43:39Z"],["dc.date.available","2019-07-09T11:43:39Z"],["dc.date.issued","2017-08-03"],["dc.description.abstract","The apicomplexan parasite Toxoplasma gondii infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with T. gondii. However, only a few hundred of them were regulated by infection and these largely diverged in neurons, SkMCs, astrocytes and fibroblasts indicating host cell type-specific transcriptional responses after infection. The heterogeneous transcriptomes of host cells before and during infection coincided with ~5,400 DEGs in T. gondii residing in different cell types. Finally, we identified gene clusters in both T. gondii and its host, which correlated with the predominant parasite persistence in neurons or SkMCs as compared to astrocytes or fibroblasts. Thus, heterogeneous expression profiles of different host cell types and the parasites' ability to adapting to them may govern the parasite-host cell interaction during toxoplasmosis."],["dc.identifier.doi","10.1038/s41598-017-07838-w"],["dc.identifier.pmid","28775382"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58935"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e45440"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Takacs, Anna C."],["dc.contributor.author","Swierzy, Izabela J."],["dc.contributor.author","Lueder, Carsten Guenter Kurt"],["dc.date.accessioned","2018-11-07T09:05:52Z"],["dc.date.available","2018-11-07T09:05:52Z"],["dc.date.issued","2012"],["dc.description.abstract","The apicomplexan parasite Toxoplasma gondii is regularly transmitted to humans via the ingestion of contaminated meat products from chronically infected livestock. This route of transmission requires intracellular development and long-term survival of the parasite within muscle tissue. In this study, we determined the cell-autonomous immunity of mature primary embryonic or C2C12 skeletal muscle cells (SkMCs) to infection with T. gondii. Non-activated SkMCs and control fibroblasts sustained parasite replication; however, interferon (IFN)-gamma significantly inhibited parasite growth in SkMCs but not in fibroblasts. Intracellular parasite replication was diminished by IFN-gamma whereas host cell invasion was not affected. Tumor necrosis factor (TNF) did not further increase the IFN-gamma-triggered host defense of SkMCs against Toxoplasma. Remarkably, IFN-gamma alone or in combination with TNF decreased the high level of T. gondii bradyzoite formation being observed in non-activated SkMCs. Stimulation of SkMCs with IFN-gamma strongly triggered expression of inducible nitric oxide synthase (iNOS) transcripts, and induced significantly higher levels of nitric oxide (NO) in SkMCs than in fibroblasts. Consequently, pharmacological inhibition of iNOS partially abrogated the IFN-gamma-induced toxoplasmacidal activity of SkMCs. In addition, SkMCs strongly up-regulated immunity-regulated GTPases (IRGs) following stimulation with IFN-gamma. IRGs accumulated on Toxoplasma-containing vacuoles in SkMCs in a parasite strain-dependent manner. Subsequent vacuole disruption and signs of degenerating parasites were regularly recognized in IFN-gamma-treated SkMCs infected with type II parasites. Together, murine SkMCs exert potent toxoplasmacidal activity after stimulation with IFN-gamma and have to be considered active participants in the local immune response against Toxoplasma in skeletal muscle."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1371/journal.pone.0045440"],["dc.identifier.isi","000308860100079"],["dc.identifier.pmid","23024821"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7936"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25422"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Interferon-gamma Restricts Toxoplasma gondii Development in Murine Skeletal Muscle Cells via Nitric Oxide Production and Immunity-Related GTPases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]