最近关键技术进步迅速,包括更广泛的单细胞“omic”方法,使免疫学家能够获得重要的新见解,以了解单个免疫细胞在保护性免疫和免疫病理学中的贡献。这些见解还告诉我们,关于免疫反应背后的(细胞)网络还有很多需要发现的地方。例如,在过去的十年里,对先天免疫的关键组成部分的研究,补充系统,已将细胞内活性补体(补体)定义为正常细胞生理学的关键协调器。这给补体的生物学增加了一个意想不到的方面,长期以来被认为是充分探索的。这里,我们将简明扼要地总结已知的补体的激活模式和功能,并提供关于细胞内补体起源的观点。我们还将提出扩展对复杂类型的评估的理由,补体基因中常见变异的个体遗传景观,对复杂的人来说,并用于重新评估已知血清补体缺乏的患者的复杂扰动。最后,我们将讨论目前在哪些方面看到的机会和障碍,以剖析补体活动的划分,从而更好地了解它们对健康和疾病中细胞功能的贡献。
Recent rapid progress in key technological advances, including the broader accessibility of single-cell \"omic\" approaches, have allowed immunologists to gain important novel insights into the contributions of individual immune cells in protective immunity and immunopathologies. These insights also taught us that there is still much to uncover about the (cellular) networks underlying immune responses. For example, in the last decade, studies on a key component of innate immunity, the complement system, have defined intracellularly active complement (the
complosome) as a key orchestrator of normal cell physiology. This added an unexpected facet to the biology of complement, which was long considered fully explored. Here, we will summarize succinctly the known activation modes and functions of the
complosome and provide a perspective on the origins of intracellular complement. We will also make a case for extending assessments of the complotype, the individual inherited landscape of common variants in complement genes, to the
complosome, and for reassessing patients with known serum complement deficiencies for
complosome perturbations. Finally, we will discuss where we see current opportunities and hurdles for dissecting the compartmentalization of complement activities toward a better understanding of their contributions to cellular function in health and disease.