PXD050258

PXD050258 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-01 01:10:01	ID requested
⏵ 1	2024-08-10 12:02:33	announced

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]

submitter keyword: Mycobacterium tuberculosis

D-serine

Rv0884c

WDR24

mTORC1

CD8+ T cell

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD050258

PRIDE project URI

• PRIDE
  1. PXD050258
     1. Label: PRIDE project
     2. Name: Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice