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2021-11-22Zeitschriftenartikel
The Redox Homeostasis of Skeletal Muscle Cells Regulates Stage Differentiation of Toxoplasma gondii
dc.contributor.authorRahman, Taibur
dc.contributor.authorSwierzy, Izabela J.
dc.contributor.authorDownie, Bryan
dc.contributor.authorSalinas, Gabriela
dc.contributor.authorBlume, Martin
dc.contributor.authorMcConville, Malcolm J.
dc.contributor.authorLüder, Carsten G. K.
dc.date.accessioned2024-07-23T14:06:09Z
dc.date.available2024-07-23T14:06:09Z
dc.date.issued2021-11-22none
dc.identifier.other10.3389/fcimb.2021.798549
dc.identifier.urihttp://edoc.rki.de/176904/11812
dc.description.abstractToxoplasma 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.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectToxoplasma gondiieng
dc.subjectstage conversioneng
dc.subjectskeletal muscleeng
dc.subjectredox homestasiseng
dc.subjecthost metabolismeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleThe Redox Homeostasis of Skeletal Muscle Cells Regulates Stage Differentiation of Toxoplasma gondiinone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11812-9
dc.type.versionpublishedVersionnone
local.edoc.container-titleFrontiers in Cellular and Infection Microbiologynone
local.edoc.container-issn2235-2988none
local.edoc.pages14none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.frontiersin.org/journals/cellular-and-infection-microbiologynone
local.edoc.container-publisher-nameFrontiers Meadia S.A.none
local.edoc.container-volume11none
local.edoc.container-reportyear2021none
dc.description.versionPeer Reviewednone

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