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cGAS/STING/TBK1/IRF3 Signaling Pathway Activates BMDCs Maturation Following Mycobacterium bovis Infection

1
College of Agriculture, Ningxia University, Xixia District, Yinchuan 750021, China
2
State Key Lab of Agrobiotechnology, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
3
College of Life Science and Engineering, Foshan University, 18 Jiangwan street, Foshan 528231, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 895; https://doi.org/10.3390/ijms20040895
Received: 4 January 2019 / Revised: 30 January 2019 / Accepted: 1 February 2019 / Published: 19 February 2019
(This article belongs to the Section Molecular Microbiology)
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Abstract

Cyclic GMP-AMP synthase (cGAS) is an important cytosolic DNA sensor that plays a crucial role in triggering STING-dependent signal and inducing type I interferons (IFNs). cGAS is important for intracellular bacterial recognition and innate immune responses. However, the regulating effect of the cGAS pathway for bone marrow-derived dendritic cells (BMDCs) during Mycobacterium bovis (M. bovis) infection is still unknown. We hypothesized that the maturation and activation of BMDCs were modulated by the cGAS/STING/TBK1/IRF3 signaling pathway. In this study, we found that M. bovis promoted phenotypic maturation and functional activation of BMDCs via the cGAS signaling pathway, with the type I IFN and its receptor (IFNAR) contributing. Additionally, we showed that the type I IFN pathway promoted CD4+ T cells’ proliferation with BMDC during M. bovis infection. Meanwhile, the related cytokines increased the expression involved in this signaling pathway. These data highlight the mechanism of the cGAS and type I IFN pathway in regulating the maturation and activation of BMDCs, emphasizing the important role of this signaling pathway and BMDCs against M. bovis. This study provides new insight into the interaction between cGAS and dendritic cells (DCs), which could be considered in the development of new drugs and vaccines against tuberculosis. View Full-Text
Keywords: Mycobacterium bovis; cGAS pathway; dendritic cells; type I interferons; CD4+ T cells Mycobacterium bovis; cGAS pathway; dendritic cells; type I interferons; CD4+ T cells
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Li, Q.; Liu, C.; Yue, R.; El-Ashram, S.; Wang, J.; He, X.; Zhao, D.; Zhou, X.; Xu, L. cGAS/STING/TBK1/IRF3 Signaling Pathway Activates BMDCs Maturation Following Mycobacterium bovis Infection. Int. J. Mol. Sci. 2019, 20, 895.

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