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Organ-specific testosterone-insensitive response of miRNA expression of C57BL/6 mice to Plasmodium chabaudi malaria

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Abstract

Increasing evidence critically implicates miRNAs in the pathogenesis of diseases, but little is known in context with infectious diseases. This study investigates as to whether the testosterone-induced persistent susceptibility to blood-stage malaria of Plasmodium chabaudi coincides with changes in miRNA expression of the anti-malaria effectors sites spleen and liver. Female C57BL/6 mice were treated with vehicle or testosterone (T) for 3 weeks. Then, T treatment was discontinued for 12 weeks before challenge with 106 P. chabaudi-parasitized erythrocytes. The miRNA expression was examined after 12 weeks of T withdrawal and during infections at peak parasitemia on day 8 p.i. using miRXplore™ microarray technology. P. chabaudi infections induce an organ-specific response of miRNA expression. We can identify 25 miRNA species to be downregulated by more than 2-fold in the spleen and 169 miRNA species in the liver. Among these 194 miRNA species, there are 12 common miRNA species that are downregulated by 0.48–0.14-fold in both spleen and liver, which are miR-194, miR-192, miR-193A-3P, miR-145, miR-16, miR-99A, miR-99B, miR-15A, miR-152, let-7G, let-7B, and miR-455-3P. Only in the liver, there is an upregulation of the miR-142-5p by 2.5-fold and miR-342-3p by 5.1-fold. After 12 weeks of T withdrawal, the spleen exhibits only the miR-200A that is upregulated by 2.7-fold. In the liver, miR-376B, miR-493*, and miR-188-3P are upregulated by 2.4-fold, 2.2-fold, and 2.1-fold, respectively, and miR-347, miR-200A, and miR-200B are downregulated by approximately 0.4-fold. Upon infection, however, these changes are not sustained, i.e., the miRNA expressions of both spleen and liver of T-pretreated mice exhibit the same response to P. chabaudi malaria as that of vehicle-treated control mice. Our data suggest (1) that the P. chabaudi-induced downregulation of miRNA expression in spleen and liver is required to allow the upregulation of their numerous target genes in response to infection, and (2) that the T-induced persistent susceptibility to P. chabaudi does not affect the responsiveness of miRNA expression in spleen and liver to blood-stage malaria.

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Acknowledgments

We are indebted to Dr. Rueberg (Miltenyi, Bergisch-Gladbach, Germany) for help with the microarray hybridizations. This research was supported by King Saud University, National Program for Science and Technology, through a grant no. (10-BIO1212-02).

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  1. Denis Delic

    Present address: Max Planck Institute for Neurological Research, Cologne, Germany

Authors and Affiliations

  1. Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia

    Saleh Al-Quraishy, Mohamed A. Dkhil & Abdel Azeem Abdel-Baki

  2. Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt

    Mohamed A. Dkhil

  3. Department of Molecular Parasitology, Heinrich-Heine University, Duesseldorf, Germany

    Denis Delic & Frank Wunderlich

  4. Department of Zoology, Faculty of Science, Beni-Suef University, Cairo, Egypt

    Abdel Azeem Abdel-Baki

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  1. Saleh Al-Quraishy
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Correspondence to Saleh Al-Quraishy.

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Fig. S1

Expression levels of hepatic miRNA species of unknown functions downregulated by P. chabaudi malaria. Green color represents downregulation as indicated in the logarithmic color scale bar shown in Fig. 2 (JPEG 458 kb)

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Table S1

Liver-specific deregulation of miRNA expression of unknown function induced by P. chabaudi malaria in vehicle-treated control mice (XLSX 16 kb)

Table S2

MicroRNA expression of spleen and liver of T-pretreated and vehicle-treated mice during P. chabaudi malaria on day 8 p.i. (XLSX 12 kb)

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Al-Quraishy, S., Dkhil, M.A., Delic, D. et al. Organ-specific testosterone-insensitive response of miRNA expression of C57BL/6 mice to Plasmodium chabaudi malaria. Parasitol Res 111, 1093–1101 (2012). https://doi.org/10.1007/s00436-012-2937-3

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