Work

Deciphering the interplay between fever and neutrophil immunometabolism during infection 2621

Year: 2025

Type: article

Abstract: Description The development of a fever is a fundamental response to infection and inflammatory diseases, yet temperature is often overlooked when studying immune development and function. Recent findings show that subsets of CD4 T cells cultured at febrile temperatures above 37 °C have altered metabolism leading to enhanced downstream effector functions, providing insight into how temperature changes affect the immune response. Neutrophils are the backbone of the innate immune response and possess an arsenal of antimicrobial processes that are crucial in the host’s response to infection. Herein, we identify that neutrophils cultured at elevated temperatures have decreased mitochondrial respiration while maintaining similar levels of glycolytic function. Since mitochondria play a critical role in regulating neutrophil effector functions, neutrophils were cultured with the bacterial pathogen Staphylococcus aureus. When neutrophils are cultured with S. aureus at febrile temperatures, neutrophils preferentially elicit phagosomal oxidative stress rather than release neutrophil extracellular traps resulting in augmented antibacterial activity. These results indicate febrile temperatures impact metabolic homeostasis within neutrophils thereby heightening the capacity of neutrophils to persist and produce an oxidative burst implying synergistic interplay between fever and oxidative stress. Funding Sources Supported by UTK startup funds; NIH 1R35GM154838 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.520