ORIGINAL PAPER
Glutaminase 1-mediated glutaminolysis regulates tuberculosis progression by modulating Th1 and Th17 immune responses
1
Department of Respiratory Medicine, Houjie Hospital of Dongguan, Dongguan, China
Submission date: 2025-02-12
Final revision date: 2025-06-26
Acceptance date: 2025-07-27
Online publication date: 2026-01-29
Corresponding author
KEYWORDS
ABSTRACT
Introduction:
Mycobacterium tuberculosis-mediated tuberculosis (TB) is an infectious disease that results in approximately 1.2 million deaths annually. Glutaminase (GLS1) is a metabolic enzyme involved in glutaminolysis. The current study examined the roles and mechanisms of GLS1 in TB progression.
Material and Methods:
Peripheral blood mononuclear cells (PBMCs) were extracted from TB patients and healthy individuals, and CD4+ T and CD14+ monocytes were sorted. PBMCs were incubated with M. tuberculosis strain H37Rv lysate to stimulate immune responses and treated with BPTES, a GLS1 inhibitor. RT-qPCR and western blotting were employed to detect mRNA and protein levels, respectively. Immunophenotyping of cells was performed using flow cytometry. ELISA was used to determine cytokine levels. Colony-forming unit assays were used to evaluate M. tuberculosis survival in macrophages. ChIP assays were used to detect the enrichment of H3K9ac/H3K27ac at the gene promoters.
Results:
GLS1 was elevated in CD4+ T cells from TB patients and H37Rv lysate-stimulated PBMCs. GLS1-mediated glutaminolysis promoted Th1 and Th17 cell differentiation. Inhibition of GLS1 by BPTES facilitated M. tuberculosis survival in macrophages. GLS1 inhibition reduced H3K9ac and H3K27ac epigenetic modification in the promoter region of interferon and interleukin 17.
Conclusions:
GLS1-mediated glutaminolysis may regulate TB progression by modulating Th1 and Th17 immune responses via epigenetic regulation.
Mycobacterium tuberculosis-mediated tuberculosis (TB) is an infectious disease that results in approximately 1.2 million deaths annually. Glutaminase (GLS1) is a metabolic enzyme involved in glutaminolysis. The current study examined the roles and mechanisms of GLS1 in TB progression.
Material and Methods:
Peripheral blood mononuclear cells (PBMCs) were extracted from TB patients and healthy individuals, and CD4+ T and CD14+ monocytes were sorted. PBMCs were incubated with M. tuberculosis strain H37Rv lysate to stimulate immune responses and treated with BPTES, a GLS1 inhibitor. RT-qPCR and western blotting were employed to detect mRNA and protein levels, respectively. Immunophenotyping of cells was performed using flow cytometry. ELISA was used to determine cytokine levels. Colony-forming unit assays were used to evaluate M. tuberculosis survival in macrophages. ChIP assays were used to detect the enrichment of H3K9ac/H3K27ac at the gene promoters.
Results:
GLS1 was elevated in CD4+ T cells from TB patients and H37Rv lysate-stimulated PBMCs. GLS1-mediated glutaminolysis promoted Th1 and Th17 cell differentiation. Inhibition of GLS1 by BPTES facilitated M. tuberculosis survival in macrophages. GLS1 inhibition reduced H3K9ac and H3K27ac epigenetic modification in the promoter region of interferon and interleukin 17.
Conclusions:
GLS1-mediated glutaminolysis may regulate TB progression by modulating Th1 and Th17 immune responses via epigenetic regulation.
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