Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity

Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41421-021-00301-1
Journal or Publication Title: Cell Discovery
Volume: 7
Number: 1
Date: 5 October 2021
Divisions: Immune-Vascular Interactions
Depositing User: General Admin
Identification Number: 10.1038/s41421-021-00301-1
ISSN: 2056-5968
Date Deposited: 07 Dec 2021 09:20
Abstract:

Pathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection.

© 2021. The Author(s).

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Yang, Hua
UNSPECIFIED
Wang, Fei
UNSPECIFIED
Guo, Xinya
UNSPECIFIED
Liu, Feng
UNSPECIFIED
Liu, Zhonghua
UNSPECIFIED
Wu, Xiangyang
UNSPECIFIED
Zhao, Mengmeng
UNSPECIFIED
Ma, Mingtong
UNSPECIFIED
Liu, Haipeng
UNSPECIFIED
Qin, Lianhua
UNSPECIFIED
Wang, Lin
UNSPECIFIED
Tang, Tianqi
UNSPECIFIED
Sha, Wei
UNSPECIFIED
Wang, Yang
UNSPECIFIED
Chen, Jianxia
UNSPECIFIED
Huang, Xiaochen
UNSPECIFIED
Wang, Jie
UNSPECIFIED
Peng, Cheng
UNSPECIFIED
Zheng, Ruijuan
UNSPECIFIED
Tang, Fen
UNSPECIFIED
Zhang, Lu
UNSPECIFIED
Wu, Chunyan
UNSPECIFIED
Oehlers, Stefan H.
UNSPECIFIED
Song, Zhigang
UNSPECIFIED
She, Jialei
UNSPECIFIED
Feng, Hua
UNSPECIFIED
Xie, Xunwei
UNSPECIFIED
Ge, Baoxue
UNSPECIFIED
Last Modified: 07 Dec 2021 09:20
URI: https://eprints.centenary.org.au/id/eprint/1176

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