Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17-92-Bim pathway in macrophages.

In order to accomplish their life cycles, intracellular pathogens, including the apicomplexan Toxoplasma gondii, subvert the innate apoptotic response of infected host cells. However, the precise mechanisms of parasite interference with the apoptotic pathway remain unclear. MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level. Using T. gondii strain TgCtwh3, which was isolated from felids and possesses the predominant genotype China 1 (ToxoDB(#)9) in China, we analyzed the miRNA expression profile of human macrophages challenged with TgCtwh3. The results showed that miR-17-92 miRNA expression was significantly increased and Bim was decreased in TgCtwh3-infected cells. Database analysis of miR-17-92 miRNAs revealed the potential binding sites in the 3'UTR of Bim, one of the crucial effectors of pro-apoptosis. Furthermore, we demonstrated that the promoter of the miR-17-92 gene cluster which encodes miRNAs was transactivated through the promoter binding of the STAT3 following TgCtwh3 infection. Taken together, we describe a novel STAT3-miR-17-92-Bim pathway, thus providing a mechanistic explanation for inhibition of apoptosis of host cells following Toxoplasma infection.