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Article

Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-κB/JNK Signaling

1
The National Key Laboratory of Agricultural Microbiology, Wuhan 430070, China
2
Key Laboratory of Pig Molecular Quantitative Genetics of Anhui Academy of Agricultural Sciences, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Hefei 230031, China
3
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
4
College of Veterinary Medicine, Murdoch University, Murdoch 6160, Australia
5
National Animal Tuberculosis Para-Reference Laboratory (Wuhan) of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China
6
Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Microorganisms 2020, 8(4), 584; https://doi.org/10.3390/microorganisms8040584
Submission received: 19 February 2020 / Revised: 14 April 2020 / Accepted: 15 April 2020 / Published: 17 April 2020
(This article belongs to the Special Issue Host–Microbe Interactions in Animal/Human Health and Disease)

Abstract

Mycobacterium tuberculosis is considered a successful pathogen with multiple strategies to undermine host immunity. The YrbE3A is encoded by Rv1964 within the RD15 region present in the genome of Mtb, but missing in M. bovis, M. bovis BCG (Pasteur) strain, and M. smegmatis (Ms). However, little is known about its function. In this study, the YrbE3A gene was cloned into pMV261 and expressed in Ms and BCG, while the strains with the vector served as the controls. The YrbE3A was expressed on the mycobacterial membrane, and the purified protein could stimulate RAW264.7 cells to produce IL-6. Furthermore, the effect of the recombinant strains on cytokine secretion by RAW264.7 was confirmed, which varied with the host strains. Ms_YrbE3A increased significantly higher levels of TNF-α and IL-6 than did Ms_vec, while BCG_YrbE3A enhanced higher TNF-α than BCG_vec. The pathways associated with NF-κB p65 and MAPK p38/JNK, other than Erk1/2, regulated this process. In addition, mice were infected with Ms_YrbE3A and Ms-vec and were kinetically examined. Compared to Ms-vec, Ms_YrbE3A induced more serious inflammatory damage, higher levels of TNF-α and IL-6, higher numbers of lymphocytes, neutrophils, and monocytes in a time-dependent way, but lower lung bacterial load in lung. These findings may contribute to a better understanding of Mtb pathogenesis.
Keywords: Mycobacterium tuberculosis; YrbE3A; macrophages; proinflammatory cytokines; signaling pathways Mycobacterium tuberculosis; YrbE3A; macrophages; proinflammatory cytokines; signaling pathways

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MDPI and ACS Style

Wang, J.; Zhu, X.; Peng, Y.; Zhu, T.; Liu, H.; Zhu, Y.; Xiong, X.; Chen, X.; Hu, C.; Chen, H.; et al. Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-κB/JNK Signaling. Microorganisms 2020, 8, 584. https://doi.org/10.3390/microorganisms8040584

AMA Style

Wang J, Zhu X, Peng Y, Zhu T, Liu H, Zhu Y, Xiong X, Chen X, Hu C, Chen H, et al. Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-κB/JNK Signaling. Microorganisms. 2020; 8(4):584. https://doi.org/10.3390/microorganisms8040584

Chicago/Turabian Style

Wang, Jieru, Xiaojie Zhu, Yongchong Peng, Tingting Zhu, Han Liu, Yifan Zhu, Xuekai Xiong, Xi Chen, Changmin Hu, Huanchun Chen, and et al. 2020. "Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-κB/JNK Signaling" Microorganisms 8, no. 4: 584. https://doi.org/10.3390/microorganisms8040584

APA Style

Wang, J., Zhu, X., Peng, Y., Zhu, T., Liu, H., Zhu, Y., Xiong, X., Chen, X., Hu, C., Chen, H., Chen, Y., & Guo, A. (2020). Mycobacterium tuberculosis YrbE3A Promotes Host Innate Immune Response by Targeting NF-κB/JNK Signaling. Microorganisms, 8(4), 584. https://doi.org/10.3390/microorganisms8040584

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