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Open AccessArticle

PP2Ac Modulates AMPK-Mediated Induction of Autophagy in Mycobacterium bovis-Infected Macrophages

1
Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
2
Department of Pathology, Faculty of Veterinary Science, Cholistan University of Veterinary and Animal Sciences, Bahawalpur 63100, Pakistan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6030; https://doi.org/10.3390/ijms20236030
Received: 25 September 2019 / Revised: 16 November 2019 / Accepted: 28 November 2019 / Published: 29 November 2019
(This article belongs to the Section Molecular Immunology)
Mycobacterium bovis (M. bovis) is the causative agent of bovine tuberculosis in cattle population across the world. Human beings are at equal risk of developing tuberculosis beside a wide range of M. bovis infections in animal species. Autophagic sequestration and degradation of intracellular pathogens is a major innate immune defense mechanism adopted by host cells for the control of intracellular infections. It has been reported previously that the catalytic subunit of protein phosphatase 2A (PP2Ac) is crucial for regulating AMP-activated protein kinase (AMPK)-mediated autophagic signaling pathways, yet its role in tuberculosis is still unclear. Here, we demonstrated that M. bovis infection increased PP2Ac expression in murine macrophages, while nilotinib a tyrosine kinase inhibitor (TKI) significantly suppressed PP2Ac expression. In addition, we observed that TKI-induced AMPK activation was dependent on PP2Ac regulation, indicating the contributory role of PP2Ac towards autophagy induction. Furthermore, we found that the activation of AMPK signaling is vital for the regulating autophagy during M. bovis infection. Finally, the transient inhibition of PP2Ac expression enhanced the inhibitory effect of TKI-nilotinib on intracellular survival and multiplication of M. bovis in macrophages by regulating the host’s immune responses. Based on these observations, we suggest that PP2Ac should be exploited as a promising molecular target to intervene in host–pathogen interactions for the development of new therapeutic strategies towards the control of M. bovis infections in humans and animals. View Full-Text
Keywords: Mycobacterium bovis (M. bovis); PP2Ac; AMPK; TKI; autophagy; macrophages Mycobacterium bovis (M. bovis); PP2Ac; AMPK; TKI; autophagy; macrophages
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Hussain, T.; Zhao, D.; Shah, S.Z.A.; Sabir, N.; Wang, J.; Liao, Y.; Song, Y.; Hussain Mangi, M.; Yao, J.; Dong, H.; Yang, L.; Zhou, X. PP2Ac Modulates AMPK-Mediated Induction of Autophagy in Mycobacterium bovis-Infected Macrophages. Int. J. Mol. Sci. 2019, 20, 6030.

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