MINI REVIEW article

Front. Immunol.

Sec. Inflammation

Lactylation modification - a bridge between sepsis and macrophage metabolic reprogramming

  • 1. Nanjing University of Chinese Medicine, Nanjing, China

  • 2. Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China

The final, formatted version of the article will be published soon.

Abstract

Sepsis is a life-threatening organ failure syndrome triggered by dysregulated host responses to infection. During disease progression, macrophages drive initial hyperinflammatory responses and critically regulate the subsequent immunosuppressive phase. Emerging evidence reveals that macrophage phenotypes dynamically adapt through metabolic reprogramming, creating phenotype-metabolism interdependence. Notably, lactate—long considered merely a glycolytic byproduct—now emerges as a key regulator through histone lactylation. This epigenetic modification fine-tunes macrophage functionality and corrects inflammatory imbalance in sepsis. This breakthrough illuminates lactylation's central role in macrophage regulation, opening new diagnostic and therapeutic avenues. This review comprehensively examines lactylation mechanisms and their impact on metabolic control in sepsis-associated macrophages.

Summary

Keywords

Glycolysis, Lactation modification, Macrophages, metabolic reprogramming, Sepsis

Received

03 November 2025

Accepted

20 February 2026

Copyright

© 2026 Fang, Xu, Zhu and Nie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Biao Xu

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Outline

Share article

Article metrics