title: Toxoplasma gondii inhibits apoptosis via a novel STAT3-miR-17-92-Bim pathway in macrophages.
abstract: 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.
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, China; Department of Immunology, Anhui Medical University, Hefei, China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Mo
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; The Central Laboratory of Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
authors.forename: Xiucai
authors.initials: X
authors.lastname: Xu
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China; The Central Laboratory of Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases Control, The Ministry of Education, Zhongshan Medical College, China; Department of Pathogen Biology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhaorong
authors.initials: Z
authors.lastname: Lun
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases Control, The Ministry of Education, Zhongshan Medical College, China; Department of Pathogen Biology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, China. Electronic address: shenjilong53@126.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D062085:RNA, Long Noncoding; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014122:Toxoplasma / Q000502:physiology*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C568997:MIR17HG, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Apoptosis; Bim; Macrophage; MicroRNA; STAT3