REVIEW article
Front. Immunol.
Sec. Inflammation
Macrophage Reprogramming and Functional Plasticity in Sepsis
Provisionally accepted
- 1Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
- 2The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Sepsis remains one of the leading causes of mortality worldwide, driven not by the infection itself but by a dysregulated host response that spirals into a cytokine storm and subsequent immune paralysis. This maladaptive immune reaction frequently culminates in life-threatening complications, including multiple organ failure and acute lung injury. Among the immune cells orchestrating this process, macrophages serve as pivotal sentinels of the innate immune system, coordinating inflammatory and reparative programs in response to microbial and endogenous cues. Increasing evidence now reveals that their behavior during sepsis is profoundly shaped by epigenetic regulation. Dynamic changes in DNA methylation, histone modifications, and non-coding RNAs fine-tune macrophage activation, polarization, and memory throughout the septic course. This review will dissect how these epigenetic programs dictate the initiation, progression, and resolution of sepsis, integrating recent discoveries to clarify underlying mechanisms and highlight promising epigenetic targets for therapeutic intervention.
Keywords: epigenetics, Immunity, Macrophages, Sepsis, therapy
Received: 24 Oct 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Huang, Cheng, Zhao and Li. 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: Min Li
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