Dataset Information

Core immunometabolic reprogramming of Mycobacterium tuberculosis-infected mouse lungs and stage-specific effects by glutamine supplementation

ABSTRACT: An emerging field of immunometabolism in tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, offers an opportunity for the development of urgently needed host-directed therapies (HDTs). Combining hypothesis-generating widely targeted metabolomics screening with transcriptome profiling in a mouse model of TB, we identify core metabolic programs and induction of signaling pathway mediated by mTORC1, the central regulator for cell metabolism, during immune cell activation. In addition to expected enhanced glycolysis and arginine biosynthesis and catabolism, induction of glutaminolysis-associated pathways, as well as serine synthesis and its catabolism by mitochondrial branch of folate cycle underscores the pivotal role of amino acids and mitochondria metabolism in orchestrating host immunity against M. tuberculosis. A further test of the hypothesis reveals that glutamine supplementation of M. tuberculosis-infected mice not only reduces lung bacillary load, but also ameliorates progression of lung pathology. Pathway analysis of transcriptomic data further unveils infection stage-specific effects of glutamine on the immunometabolic response of immune cells. Glutamine bolsters host protective immunity during the chronic phase of infection by promoting core metabolic pathways, including glycolysis, while attenuating the overall host immune response during the acute phase. Collectively, the data emphasize the central role of amino acid and mitochondrial metabolism, in concert with other signaling and metabolic pathways, including glycolysis, in meeting the demand of activating immune cells for energy, signaling molecules, and anabolic precursors. These novel observations will provide therapeutic strategies for the development of novel HDTs for TB treatment by targeting specific metabolic pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE255689 | GEO | 2026/02/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact on human and animal health worldwide. Mycobacterial life cycle is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals when compared to uninfected controls are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls but protein levels increased as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggested that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recover to limit pathogen multiplication and promote survival that also facilitates pathogen transmission.

Dataset Information

Core immunometabolic reprogramming of Mycobacterium tuberculosis-infected mouse lungs and stage-specific effects by glutamine supplementation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets