Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway

Hasan Alghetaa; Amira Mohammed; Narendra Singh; Kiesha Wilson; Goushuai Cai; Nagireddy Putluri; Mitzi Nagarkatti; Prakash Nagarkatti

doi:10.3389/fphar.2023.1106733

Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway

Front Pharmacol. 2023 Feb 24:14:1106733. doi: 10.3389/fphar.2023.1106733. eCollection 2023.

Authors

Hasan Alghetaa¹, Amira Mohammed¹, Narendra Singh², Kiesha Wilson², Goushuai Cai³, Nagireddy Putluri⁴, Mitzi Nagarkatti², Prakash Nagarkatti²

Affiliations

¹ Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq.
² Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
³ Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States.
⁴ Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, United States.

Abstract

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Keywords: ARDS (acute respiratory disease syndrome); MiR-100; ScRNA; T-cell metabolism; mTOR; metabolome; resveratrol; staphylococcal enterotoxin B (SEB).

Abstract

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