Les métabokines, des médiateurs essentiels de l’immunité anti-infectieuse

Cezard, Adeline; Monard, Sarah; Bréa-Diakite, Deborah; Guillon, Antoine; Si‐Tahar, Mustapha

doi:10.1051/medsci/2021031

Cited by 5 publications

(1 citation statement)

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“…In M1 pro-inflammatory macrophages, it has already been said that stopping the TCA causes the modification of the metabolism with citrate which no longer participates in the TCA but joins the cycle of PPP. 58 Succinate, which activates hypoxia-inducible factor-α (HIF1-α), could be one of the causes of the metabolism change, as HIF1-α promotes glycolysis and PPP. 46 IFN-γ and TNF-α also cause damage to mitochondria via the reduction of mitochondrial membrane potential (ΔΨm) and the decrease in mitochondrial DNA.…”

Section: Ifn-γ and Tnf-α And Energy Generationmentioning

confidence: 99%

Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy

Nunes,

Roda,

Andrieux

et al. 2023

Exp Biol Med (Maywood)

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Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease affecting around 6 million people. About 30% of CD patients develop chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy that occurs decades after the initial infection, while most infected patients (60%) remain asymptomatic in the so-called indeterminate form (IF). Death results from heart failure or arrhythmia in a subset of CCC patients. Myocardial fibrosis, inflammation, and mitochondrial dysfunction are involved in the arrhythmia substrate and triggering events. Survival in CCC is worse than in other cardiomyopathies, which may be linked to a Th1-T cell rich myocarditis with abundant interferon (IFN)-γ and tumor necrosis factor (TNF)-α, selectively lower levels of mitochondrial energy metabolism enzymes in the heart, and reduced levels of high-energy phosphate, indicating poor adenosine triphosphate (ATP) production. IFN-γ and TNF-α signaling, which are constitutively upregulated in CD patients, negatively affect mitochondrial function in cardiomyocytes, recapitulating findings in CCC heart tissue. Genetic studies such as whole-exome sequencing (WES) in nuclear families with multiple CCC/IF cases has disclosed rare heterozygous pathogenic variants in mitochondrial and inflammatory genes segregating in CCC cases. In this minireview, we summarized studies showing how IFN-γ and TNF-α affect cell energy generation, mitochondrial health, and redox homeostasis in cardiomyocytes, in addition to human CD and mitochondria. We hypothesize that cytokine-induced mitochondrial dysfunction in genetically predisposed patients may be the underlying cause of CCC severity and we believe this mechanism may have a bearing on other inflammatory cardiomyopathies.

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Section: Ifn-γ and Tnf-α And Energy Generationmentioning

confidence: 99%