REVIEW article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicMetabolic Implications in Sepsis and Inflammation-related Critical IllnessesView all 12 articles
Crosstalk of Mitochondrial Dysfunction and Macrophage Polarization in Sepsis
Provisionally accepted
- 1Second Affiliated Hospital of Jilin University, Changchun, China
- 2The Second Hospital of Jilin University, Changchun, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Sepsis is a complex condition marked by significant dysregulation of immune and metabolic processes, leading to multi-organ failure. Macrophages, key mediators of immune activity, demonstrate functional flexibility by switching between pro-and anti-inflammatory phenotypes in response to inflammatory and metabolic signals in their local environment. During sepsis, pathogen-derived signals activate host defense responses that impair intercellular oxygen transport, increase oxygen consumption by immune cells within inflamed tissues, and promote a metabolic transition toward aerobic glycolysis. This metabolic transition supports immune defense mechanisms, and the metabolic by-products further regulate immune activation through feedback in key signaling cascades, promoting a transition toward tolerance during the resolution phase. Since mitochondria are central hubs for cellular energy homeostasis, they play a crucial role in this process. Mitochondrial dysfunction and metabolic changes are now recognized as major contributors to the progression of sepsis. The accumulation of mitochondria-derived metabolites can further modulate immune signaling pathways, actively influencing macrophage function. Therefore, this review emphasizes the crosstalk between macrophage polarization and mitochondrial changes, with a focus on new molecular insights and the potential of mitochondrial pathways as biomarkers or therapeutic targets. These concepts provide a foundation for advancing both experimental research and clinical applications, potentially guiding future interventions to better manage sepsis and its associated mortalities.
Keywords: crosstalk, Macrophage polarization, metabolic adaptation, Mitochondrial dysfunction, Sepsis
Received: 25 Aug 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Zhang, Zhang, Ji and Zhang. 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: Jingxiao Zhang
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.