کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2436269 | 1107296 | 2012 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Host metabolism regulates growth and differentiation of Toxoplasma gondii Host metabolism regulates growth and differentiation of Toxoplasma gondii](/preview/png/2436269.png)
A critical step in the pathogenesis of Toxoplasma gondii is conversion from the fast-replicating tachyzoite form experienced during acute infection to the slow-replicating bradyzoite form that establishes long-lived tissue cysts during chronic infection. Bradyzoite cyst development exhibits a clear tissue tropism in vivo, yet conditions of the host cell environment that influence this tropism remain unclear. Using an in vitro assay of bradyzoite conversion, we have found that cell types differ dramatically in the ability to facilitate differentiation of tachyzoites into bradyzoites. Characterization of cell types that were either resistant or permissive for conversion revealed that resistant cell lines release low molecular weight metabolites that could support tachyzoite growth under metabolic stress conditions and thereby inhibit bradyzoite formation in permissive cells. Biochemical analysis revealed that the glycolytic metabolite lactate is an inhibitory component of supernatants from resistant cells. Furthermore, upregulation of glycolysis in permissive cells through the addition of glucose or by overexpression of the host kinase, Akt, was sufficient to convert cells from a permissive to a resistant phenotype. These results suggest that the metabolic state of the host cell may play a role in determining the predilection of the parasite to switch from the tachyzoite to bradyzoite form.
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► Host cells are either permissive or resistant for Toxoplasma gondii stage conversion.
► Resistant cells release soluble mediators that inhibit conversion in trans.
► Lactate was identified an inhibitory mediator released from resistant cells.
► Enhancing glycolysis in permissive cells converted them to a resistant phenotype.
Journal: International Journal for Parasitology - Volume 42, Issue 10, September 2012, Pages 947–959