Resveratrol Attenuates Staphylococcal Enterotoxin B-Activated Immune Cell Metabolism

Authors

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

Publication Date

1-1-2023

Journal

Frontiers in Pharmacology

DOI

10.3389/fphar.2023.1106733

PMID

36909201

PMCID

PMC9999031

PubMedCentral® Posted Date

2-24-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

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

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.

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