# Glucose Metabolism and Innate Immune Responses in Influenza Virus Infection: Mechanistic Insights and Clinical Perspectives

## TL;DR

This paper explores how glucose metabolism influences immune responses during influenza infection and suggests targeting metabolic pathways as a potential treatment strategy.

## Contribution

The paper provides mechanistic insights into immune-metabolic crosstalk during influenza and proposes metabolic checkpoints as novel therapeutic targets.

## Key findings

- The Warburg effect and PFK1/PFKFB3 enzyme complex are key in glycolytic shifts during influenza infection.
- mTOR signaling promotes glycolysis and regulates inflammatory cytokine production in immune cells.
- Modulating metabolic changes could influence disease progression and improve immunotherapy for influenza.

## Abstract

This review article discusses glucose metabolic alterations affecting immune cell responses to influenza virus infection. It highlights possible relationships between essential metabolic targets and influenza replication dynamics in immune cells. Thus, kinases as essential regulators of glucose metabolism as well as critical immune mediators during this infection such as interferons, tumor necrosis factor-alpha and transforming growth factor beta have been illustrated. Mechanistic highlights are provided for both the Warburg effect, where glycolysis shifts to lactate production during influenza infection, and the PFK1/PFKFB3 enzyme complex as the rate-determining regulator of glycolysis whose activity increases during the course of influenza infection. The mechanisms of mammalian target of rapamycin (mTOR) signaling as a promotor of glycolysis and a regulator of inflammatory cytokine production are discussed across various immune cell types during infection. We conclude that modulation of the metabolic changes associated with immune responses plays an important role in disease progression, and that targeting metabolic checkpoints or kinases may offer promising avenues for future immunotherapy approaches for the treatment of influenza virus infection. We also emphasize the need for further research to develop a comprehensive biological model that clarifies host outcomes and the complex nature of immune-metabolic regulation and crosstalk.