Dataset Information

CTH exacerbates Helicobacter pylori immunopathogenesis by promoting macrophage metabolic remodeling and activation

ABSTRACT: Macrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world's population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme, cystathionine g-lyase (CTH), is upregulated in humans and mice with H. pylori infection. Here we show that induction of CTH in macrophages by H. pylori promotes persistent inflammation. Cth-/- mice have reduced macrophage and T-cell activation in H. pylori-infected tissues, an altered metabolome, and decreased enrichment of immune-associated gene networks, culminating in decreased H. pylori-induced-gastritis. CTH is downstream of the proposed anti-inflammatory molecule, S-adenosylmethionine (SAM). While Cth-/- mice exhibit gastric SAM accumulation, WT mice treated with SAM did not display protection against H. pylori-induced inflammation. Instead, we demonstrate that Cth-deficient macrophages exhibit alterations in the proteome, decreased NF-kB activation, diminished expression of macrophage activation markers, and impaired oxidative phosphorylation and glycolysis. Thus, through altering cellular respiration, CTH is a key enhancer of macrophage activation contributing to a pathogenic inflammatory response that is the universal precursor for the development of H. pylori-induced gastric disease.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

SUBMITTER: M. Wade Calcutt

PROVIDER: MTBLS2851 | MetaboLights | 2022-06-14

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS2851	Other
	FILES	Other
	a_MTBLS2851_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS2851_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	files-all.json	Other

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Publications

Cystathionine γ-lyase exacerbates Helicobacter pylori immunopathogenesis by promoting macrophage metabolic remodeling and activation.

Latour Yvonne L YL Sierra Johanna C JC Finley Jordan L JL Asim Mohammad M Barry Daniel P DP Allaman Margaret M MM Smith Thaddeus M TM McNamara Kara M KM Luis Paula B PB Schneider Claus C Jacobse Justin J Goettel Jeremy A JA Calcutt M Wade MW Rose Kristie L KL Schey Kevin L KL Milne Ginger L GL Delgado Alberto G AG Piazuelo M Blanca MB Paul Bindu D BD Snyder Solomon H SH Gobert Alain P AP Wilson Keith T KT

JCI insight 20220622 12

Macrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world's population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme cystathionine γ-lyase (CTH) is upregulated in humans and mice with H. pylori infection. Here, we show that induction of CTH in macrophages by ...[more]

PMID: 35579952

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