Inhibition of glycolysis in tuberculosis-mediated metabolic rewiring reduces HIV-1 spread across macrophages - I2MC
Pré-Publication, Document De Travail Année : 2024

Inhibition of glycolysis in tuberculosis-mediated metabolic rewiring reduces HIV-1 spread across macrophages

Résumé

Tuberculosis (TB) is a significant aggravating factor in individuals living with human immunodeficiency virus type 1 (HIV-1), the causative agent for acquired immunodeficiency syndrome (AIDS). Both Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB, and HIV-1 target macrophages. Understanding how Mtb subverts these cells may facilitate the identification of new druggable targets. Here, we explored how TB can induce macrophages to form tunneling nanotubes (TNT), promoting HIV-1 spread. We found that TB triggers metabolic rewiring of macrophages, increasing their glycolytic ATP production. Using pharmacological inhibitors and glucose deprivation, we discovered that disrupting aerobic glycolysis significantly reduces HIV-1 exacerbation in these macrophages. Glycolysis is essential for tunneling nanotubes (TNT) formation, which facilitates viral transfer and cell-tocell fusion and induces the expression of the sialoadhesin Siglec-1, enhancing both HIV-1 binding and TNT stabilization. Glycolysis did not exacerbate HIV-1 infection when TNT formation was pharmacologically prevented, indicating that higher metabolic activity is not sufficient per se to make macrophages more susceptible to HIV-1. Overall, these data might facilitate the development of targeted therapies aimed at inhibiting glycolytic activity in TBinduced immunomodulatory macrophages to ultimately halt HIV-1 dissemination in co-infected patients.

Domaines

Immunologie
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Dates et versions

hal-04739994 , version 1 (16-10-2024)

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Zoï Vahlas, Natacha Faivre, Sarah C Monard, Quentin Hertel, Mariano Maio, et al.. Inhibition of glycolysis in tuberculosis-mediated metabolic rewiring reduces HIV-1 spread across macrophages. 2024. ⟨hal-04739994⟩
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