Characterization of mouse brain microRNAs after infection with cyst-forming Toxoplasma gondii

Particle and Fibre Toxicology

Xing-Quan Zhu²  Yi-Fan Fan³  Si-Yang Huang¹  Alasdair J Nisbet⁴  Dong-Hui Zhou¹  Min-Jun Xu¹ 

[1]State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China

[2]College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang Province, 163319, PR China

[3]College of Veterinary Medicine, Sichuan Agricultural University, Ya’an, Sichuan Province, 625014, PR China

[4]Vaccines and Diagnostics, Moredun Research Institute, Pentlands Science Park, Midlothian, Scotland, EH26 0PZ, UK

关键词: Host regulation;    Brain;    Mouse;    MicroRNA (miRNA);    Toxoplasmosis;    Toxoplasma gondii;   

Others  :  1227028
DOI  :  10.1186/1756-3305-6-154

 received in 2013-04-16, accepted in 2013-05-19,  发布年份 2013

【 摘 要 】

Background

The obligate intracellular parasite Toxoplasma gondii can interfere with host cell signaling pathways, alter host defense systems and cell cycle control, and establish a chronic infection in the central nervous system. T. gondii infection may alter the expression profile of host microRNAs (miRNAs) which have key regulatory functions at the post-transcriptional level.

Methods

Using high-throughput sequencing and real-time quantitative PCR technology, we compared the miRNA expression profiles of uninfected mouse brains with brains from mice at 14 days and 21 days after infection with cyst-forming T. gondii (Type II).

Results

A total of 51.30 million raw reads were obtained from all samples and 495 (14d infected mouse sample), 511 (14d sham-infected control), 504 (21d infected mouse sample) and 514 (21d sham-infected control) miRNA candidates identified. Among these, 414 miRNAs were consistent across all the studied groups, 17 were specific to the 14d infected group and 32 were specific to the 21d infected group. In addition, 9 miRNAs were common to both the 14d- and 21d-infected groups. Enrichment analysis for the targets of these miRNAs showed a high percentage of “protein tag” functions. Immune related targets including chemokines, cytokines, growth factors and interleukins were also found.

Conclusions

These results not only showed that the miRNA expression of the host can be changed by the invasion of cyst-forming T. gondii, but also indicated that the host attempts to respond using two tactics: marking proteins with “protein tags” and adaptation of immune related systems.

【 授权许可】

   
2013 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Dubey JP: Toxoplasmosis of Animals and Humans. Boca Raton, Florida: CRC Press; 2010:313.
• [2]Nardoni S, Angelici MC, Mugnaini L, Mancianti F: Prevalence of Toxoplasma gondii infection in Myocastor coypus in a protected Italian wetland. Parasit Vectors 2011, 4:240. BioMed Central Full Text
• [3]Chen J, Xu MJ, Zhou DH, Song HQ, Wang CR, Zhu XQ: Canine and feline parasitic zoonoses in China. Parasit Vectors 2012, 5:152. BioMed Central Full Text
• [4]Tian YM, Dai FY, Huang SY, Deng ZH, Duan G, Zhou DH, Yang JF, Weng YB, Zhu XQ, Zou FC: First report of Toxoplasma gondii seroprevalence in peafowls in Yunnan Province. Southwestern China. Parasit Vectors 2012, 5:205. BioMed Central Full Text
• [5]Zhou P, Chen Z, Li HL, Zheng H, He S, Lin RQ, Zhu XQ: Toxoplasma gondii infection in humans in China. Parasit Vectors 2011, 4:165. BioMed Central Full Text
• [6]Montoya JG, Liesenfeld O: Toxoplasmosis. Lancet 2004, 363:1965-1976.
• [7]Sibley LD, Boothroyd JC: Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature 1992, 359:82-85.
• [8]Olguin-Lamas A, Madec E, Hovasse A, Werkmeister E, Callebaut I, Slomianny C, Delhaye S, Mouveaux T, Schaeffer-Reiss C, Van Dorsselaer A, Tomavo S: A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence. PLoS Pathog 2011, 7:e1001328.
• [9]Boothroyd JC, Dubremetz JF: Kiss and spit: the dual roles of Toxoplasma rhoptries. Nat Rev Microbiol 2008, 6:79-88.
• [10]Saeij JP, Boyle JP, Coller S, Taylor S, Sibley LD, Brooke-Powell ET, Ajioka JW, Boothroyd JC: Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 2006, 314:1780-1783.
• [11]Saeij JP, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC: Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 2007, 445:324-327.
• [12]Molestina RE, El-Guendy N, Sinai AP: Infection with Toxoplasma gondii results in dysregulation of the host cell cycle. Cell Microbiol 2008, 10:1153-1165.
• [13]Du T, Zamore PD: Beginning to understand microRNA function. Cell Res 2007, 17:661-663.
• [14]Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP: Vertebrate microRNA genes. Science 2003, 299:1540.
• [15]Liu Q, Tuo W, Gao H, Zhu XQ: MicroRNAs of parasites: current status and future perspectives. Parasitol Res 2010, 107:501-507.
• [16]Lin WC, Li SC, Lin WC, Shin JW, Hu SN, Yu XM, Huang TY, Chen SC, Chen HC, Chen SJ, Huang PJ, Gan RR, Chiu CH, Tang P: Identification of microRNA in the protist Trichomonas vaginalis. Genomics 2009, 93:487-493.
• [17]TenOever BR: RNA viruses and the host microRNA machinery. Nat Rev Microbiol 2013, 11:169-180.
• [18]Zhai H, Fesler A, Ju J: MicroRNA: a third dimension in autophagy. Cell Cycle 2013, 12:246-250.
• [19]Zeiner GM, Norman KL, Thomson JM, Hammond SM, Boothroyd JC: Toxoplasma gondii infection specifically increases the levels of key host microRNAs. PLoS One 2010, 5:e8742.
• [20]Weiss LM, Kim K: The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci 2000, 5:D391-D405.
• [21]Bohne W, Holpert M, Gross U: Stage differentiation of the protozoan parasite Toxoplasma gondii. Immunobiology 1999, 201:248-254.
• [22]Thirugnanam S, Rout N, Gnanasekar M: Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs. Infect Agent Cancer 2013, 8:8. BioMed Central Full Text
• [23]Zhou DH, Zhao FR, Huang SY, Xu MJ, Song HQ, Su C, Zhu XQ: Changes in the proteomic profiles of mouse brain after infection with cyst-forming Toxoplasma gondii. Parasit Vectors 2013, 6:96. BioMed Central Full Text
• [24]Xu MJ, Liu Q, Nisbet AJ, Cai XQ, Yan C, Lin RQ, Yuan ZG, Song HQ, He XH, Zhu XQ: Identification and characterization of microRNAs in Clonorchis sinensis of human health significance. BMC Genomics 2010, 11:521. BioMed Central Full Text
• [25]Li R, Yu C, Li Y, Lam TW, Yiu SM, Kristiansen K, Wang J: SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 2009, 25:1966-1967.
• [26]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120:15-20.
• [27]Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP: MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007, 27:91-105.
• [28]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005, 33:e179.
• [29]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001, 25:402-408.
• [30]Harcus YM, Parkinson J, Fernandez C, Daub J, Selkirk ME, Blaxter ML, Maizels RM: Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites. Genome Biol 2004, 5:R39. BioMed Central Full Text
• [31]Akbari MF, Pieters R, den Boer ML: The hunting of targets: challenge in miRNA research. Leukemia 2013, 27:16-23.
• [32]Djurkovic-Djakovic O, Djokic V, Vujanic M, Zivkovic T, Bobic B, Nikolic A, Slavic K, Klun I, Ivovic V: Kinetics of parasite burdens in blood and tissues during murine toxoplasmosis. Exp Parasitol 2012, 131:372-376.
• [33]Del RL, Butcher BA, Bennouna S, Hieny S, Sher A, Denkers EY: Toxoplasma gondii triggers myeloid differentiation factor 88-dependent IL-12 and chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct parasite molecules and host receptors. J Immunol 2004, 172:6954-6960.
• [34]Hardison JL, Wrightsman RA, Carpenter PM, Kuziel WA, Lane TE, Manning JE: The CC chemokine receptor 5 is important in control of parasite replication and acute cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun 2006, 74:135-143.
• [35]Gazzinelli RT, Ropert C, Campos MA: Role of the Toll/interleukin-1 receptor signaling pathway in host resistance and pathogenesis during infection with protozoan parasites. Immunol Rev 2004, 201:9-25.
• [36]Finkelman FD, Shea-Donohue T, Morris SC, Gildea L, Strait R, Madden KB, Schopf L, Urban JJ: Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol Rev 2004, 201:139-155.