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Cellular Prion Protein Participates in the Regulation of Inflammatory Response and Apoptosis in BV2 Microglia During Infection with Mycobacterium bovis

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Abstract

The cellular prion protein (PrPC) is a glycoprotein anchored by glycosylphosphatidylinositol to the cell surface and is abundantly expressed in the central nervous system. A previous study has shown that PrPC contributes to the establishment of infections with intracellular bacteria in macrophages. In the present work, we investigated the role of PrPC in the response of BV2 microglia to Mycobacterium bovis infection. For this purpose, we examined the mRNA expression of prion protein gene (PRNP) upon M. bovis infection and analyzed the effect of siRNA-mediated disruption of PRNP on different parameters of microglial activation and apoptosis in M. bovis-infected microglia. We found that M. bovis infection induced a gradual increase in PRNP mRNA level and that siRNA-mediated silencing of PRNP in M. bovis-infected microglia reduced M. bovis-induced upregulation of pro-inflammatory factors, increased the rate of apoptosis in infected microglia, promoted the intrinsic apoptotic pathway, and downregulated the extrinsic apoptotic pathway. We conclude that PrPC participates in the regulation of the response of microglia to M. bovis infection through the upregulation of pro-inflammatory cytokines and the modulation of apoptosis by interference with the intrinsic apoptotic pathway.

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Abbreviations

PrP:

Prion protein

PrPC :

Cellular prion protein

PrPSc :

Pathogenic prion protein

PRNP :

Prion protein gene

CNS:

Central nervous system

M. bovis :

Mycobacterium bovis

TB:

Tuberculosis

GPI:

Glycosylphosphatidylinositol

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Acknowledgments

This work was supported by the Natural Science Foundation of China (Project No. 30972164, No. 31001048, No. 31172293, and No. 31272532), the Special Scientific Fund for Nonprofit Public Industry (Agriculture), China (Project No. 200903027), and the Beijing Science Foundation of China (Project No. 6101002).

Conflict of Interest

The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China

    Tianjian Ding, Xiangmei Zhou, Mohammed Kouadir, Fushan Shi, Yang Yang, Jin Liu, Min Wang, Xiaomin Yin, Lifeng Yang & Deming Zhao

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  1. Tianjian Ding
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  2. Xiangmei Zhou
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  3. Mohammed Kouadir
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  4. Fushan Shi
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  5. Yang Yang
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  6. Jin Liu
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  7. Min Wang
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  8. Xiaomin Yin
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  9. Lifeng Yang
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  10. Deming Zhao
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Correspondence to Deming Zhao.

Additional information

Tianjian Ding and Xiangmei Zhou contributed equally to this work.

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Ding, T., Zhou, X., Kouadir, M. et al. Cellular Prion Protein Participates in the Regulation of Inflammatory Response and Apoptosis in BV2 Microglia During Infection with Mycobacterium bovis . J Mol Neurosci 51, 118–126 (2013). https://doi.org/10.1007/s12031-013-9962-2

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