STAT3-dependent transactivation of miRNA genes following Toxoplasma gondii infection in macrophage

Background: the apicomplexan parasite toxoplasma gondii can infect and replicate in virtually any nucleated cell in many species of warm-blooded animals; t. gondii has elaborate mechanisms to counteract host-cell apoptosis in order to maintain survival and breed in the host cells. methods. using microarray profiling and a combination of conventional molecular approaches,we investigated the levels of micrornas (mirnas) in human macrophage during t. gondii infection. we used molecular tools to examine toxoplasma-upregualted mirnas to revealed potential signal transducers and activators of transcription 3(stat3) binding sites in the promoter elements of a subset of mirna genes. we analysed the apoptosis of human macrophage with the functional inhibition of the stat3-binding mirnas by flow cytometry. results: our results demonstrated differential alterations in the mature mirna expression profile in human macrophage following t. gondii infection. database analysis of toxoplasma-upregulated mirnas revealed potential stat3 binding sites in the promoter elements of a subset of mirna genes. we demonstrated that mir-30c-1,mir-125b-2,mir-23b-27b-24-1 and mir-17 ∼ 92 cluster genes were transactivated through promoter binding of the stat3 following t. gondii infection. importantly,functional inhibition of selected stat3-binding mirnas in human macropahges increased apoptosis of host cells. conclusions: a panel of mirnas is regulated through promoter binding of the stat3 in human macrophage and these mirnas are involved in anti-apoptosis in response to t. gondii infection. © 2013 cai et al.; licensee biomed central ltd.