Keeping It All Going-Complement Meets Metabolism.
Keeping It All Going-Complement Meets Metabolism.
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DOI：
10.3389/fimmu.2017.00001
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发表时间：
2017
影响因子：
7.3
通讯作者：
Kemper C
中科院分区：
文献类型：
--
作者：
Kolev M;Kemper C
补体系统是先天免疫的一个进化上古老而重要的组成部分，是检测和清除入侵病原体的关键。它最初被发现为在血清、淋巴和间质液中循环的肝源性哨兵系统，介导细菌、真菌和病毒的调理作用和裂解杀伤以及一般炎症反应的启动。尽管在过去的五十年里，补体也被认为是适应性免疫的关键指导者，这表明补体的功能可能比最初预期的更广泛，但研究人员和临床医生的主要观点是，补体的关键功能在原则上是确定的。然而，现在越来越多的人认识到，补体活性远远超出了“经典”免疫功能，并且该系统也是正常（神经元）发育和活性以及一般细胞和组织完整性和稳态所需的。此外，最近的发现，补体激活不限于细胞外空间，但发生在细胞内，导致令人惊讶的理解，补体参与细胞的基本过程的调节，特别是那些代谢性质的，主要是通过补体和细胞内传感器之间的新串扰，效应器，途径，已被忽视，因为它们的空间分离。该领域的这些范式转变导致了补体研究的复兴，并提供了新的平台，以更好地了解补体功能在免疫及其他方面广泛影响的分子途径。在这篇综述中，我们将涵盖目前的知识补体的新兴关系的细胞代谢机制，重点是血清循环与细胞内活性补体在正常细胞存活和诱导效应功能的功能差异。我们还将讨论如何更仔细地研究关键补体成分的演变，不仅使补体和代谢之间的功能联系相当“可预测”，但它也可能为发现补体在基本细胞过程中的其他作用提供线索。
The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity—indicating that complement’s function is likely broader than initially anticipated—the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond “classic” immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature—mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement’s emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also discuss how taking a closer look into the evolution of key complement components not only made the functional connection between complement and metabolism rather “predictable” but how it may also give clues for the discovery of additional roles for complement in basic cellular processes.