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病毒性肺炎的免疫病理损伤与肺泡巨噬细胞（Alveolar macrophages, AMs）的极化失衡密切相关，而线粒体代谢重编程是AMs功能表型调控的核心机制之一，AMs可通过动态切换代谢模式，调节极化平衡，从而调控免疫应答强度，而极化状态又通过细胞因子和信号分子反馈调节线粒体代谢活性，这种相互作用在病毒性肺炎中既参与抗病毒防御，又可能介导免疫病理损伤。病毒作用于AMs线粒体代谢的关键节点，干扰代谢-免疫平衡，导致AMs发生M1和M2型极化，从而进入不同的代谢状态；不同极化状态下的AMs又能够通过合成不同的细胞因子对线粒体的代谢模式进行反馈调节。因此，靶向AMs线粒体代谢相关靶点，调节AMs极化平衡，有利于促进肺部炎症消散和肺组织修复过程的平衡，是病毒性肺炎相关药物研发的重要方向。对此，本文分别总结了AMs极化与线粒体代谢过程的相互调控机制及其在病毒性肺炎发病机制中的作用，以期深入揭示病毒感染后，宿主代谢-免疫微环境的整体调节规律，并进一步阐明中药多通路、多靶点的特性在调控代谢-免疫平衡治疗病毒性肺炎中的优势所在，为中药抗病毒新药的研发提供参考。
Abstract：Alveolar macrophages(AMs) play a pivotal role in host antiviral immunity and immune-mediated lung injury during viral pneumonia. Dysregulated AM polarization is tightly linked to immune-pathological damage, while mitochondrial metabolic reprogramming serves as a central determinant of AM functional phenotypes. AMs dynamically shift between metabolic programs to modulate polarization states and fine-tune immune responses. Conversely, distinct polarization states feed back to reshape mitochondrial activity through cytokines and signaling mediators. This bidirectional interaction supports antiviral defense yet may also amplify immunopathology in viral pneumonia. Viruses can hijack key nodes of mitochondrial metabolism in AMs, disrupting metabolic-immune homeostasis and driving M1-or M2-biased polarization with corresponding metabolic profiles. Polarized AMs further influence mitochondrial metabolism through differential cytokine synthesis, forming a metabolic– immune regulatory loop. Targeting AM mitochondrial metabolic pathways to rebalance polarization represents a promising strategy for alleviating pulmonary inflammation and promoting tissue repair, thus holding substantial value for antiviral drug innovation. This review summarizes the regulatory mechanisms governing AM polarization and mitochondrial metabolism, and highlights their roles in the pathogenesis of viral pneumonia. We further discuss recent advances in traditional Chinese medicine(TCM), emphasizing its multitarget, multipathway regulatory advantages in restoring metabolic – immune homeostasis during viral pneumonia. These insights provide a theoretical foundation for the development of novel TCMbased antiviral therapies.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250290
中图分类号:R259
引用信息:
[1]崔羲和,孙绮悦,谢锐,等.肺泡巨噬细胞极化与线粒体代谢重编程在病毒性肺炎中的相互作用机制及中医药治疗的研究进展[J].病毒学报,2025,41(06):1766-1774.DOI:10.13242/j.cnki.bingduxuebao.250290.
基金信息:
道地药材品质保障与资源持续利用全国重点实验室“重大科技创新”专项（CI2024E003KC-14）~~