PXD050258 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice |
Description | Interferon (IFN)-γ-producing CD8+ T cells are involved in control of Mycobacterium tuberculosis (Mtb) infection, in part by promoting antimicrobial activities of macrophages. Whether Mtb counters these responses, particularly during the hypoxic conditions that arise within granulomas during infection, remains unknown. Using metabolomic, proteomic and genetic approaches, here we show that Mtb induces Rv0884c (SerC), a Mtb phosphoserine aminotransferase, to produce D-serine. This activity increased Mtb pathogenesis in mice but did not directly affect intramacrophage Mtb survival. Instead, D-serine inhibited IFN-γ production by CD8+ T cells, which indirectly reduced the ability of macrophages to restrict Mtb upon coculture. Mechanistically, D-serine interacted with WDR24, a subunit of GATOR2, and inhibited mTORC1 activation in T cells. This decreased T-bet transcription factor expression by CD8+ T cells and reduced IFN-γ production. Our findings suggest a mechanism of mycobacterial metabolic adaptation to hypoxia which leads to amino acid-dependent suppression of adaptive anti-TB immunity. |
HostingRepository | PRIDE |
AnnounceDate | 2024-08-10 |
AnnouncementXML | Submission_2024-08-10_12:02:32.908.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hongyu Cheng |
SpeciesList | scientific name: Mycobacterium tuberculosis OFXR-32; NCBI TaxID: 1402601; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-03-01 01:10:01 | ID requested | |
⏵ 1 | 2024-08-10 12:02:33 | announced | |
Publication List
10.1038/s41564-024-01701-1; |
Cheng H, Ji Z, Wang Y, Li S, Tang T, Wang F, Peng C, Wu X, Cheng Y, Liu Z, Ma M, Wang J, Huang X, Wang L, Qin L, Liu H, Chen J, Zheng R, Feng CG, Cai X, Qu D, Ye L, Yang H, Ge B, T cell-dependent immunity in mice. Nat Microbiol, 9(7):1856-1872(2024) [pubmed] |
Keyword List
submitter keyword: Mycobacterium tuberculosis |
D-serine |
Rv0884c |
WDR24 |
mTORC1 |
CD8+ T cell |
Contact List
Baoxue Ge |
contact affiliation | 1 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, PR China 2 Department of Microbiology and Immunology, Tongji University School of Medicine, Shanghai 200049, PR China 3 Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. |
contact email | gebaoxue@sibs.ac.cn |
lab head | |
Hongyu Cheng |
contact affiliation | Tongji University |
contact email | 2010604@tongji.edu.cn |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050258
- Label: PRIDE project
- Name: Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice