Abstract 摘要
Bacteriophages—viruses that infect bacteria—are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize what is currently known about our phageome and its interactions with the immune system. We first review how phages indirectly affect immunity via bacterial expression of phage-encoded proteins. We next review how phages directly influence innate immunity and bacterial clearance. Finally, we discuss adaptive immunity against phages and its implications for phage/bacterial interactions. In light of these data, we propose that our microbiome can be understood as an interconnected network of bacteria, bacteriophages, and human cells and that the stability of these tri-kingdom interactions may be important for maintaining our immunologic and metabolic health. Conversely, the disruption of this balance, through exposure to exogenous phages, microbial dysbiosis, or immune dysregulation, may contribute to disease.
噬菌体–感染细菌的病毒–在人体内大量存在，但它们对人类健康的意义才刚刚开始探索。在此，我们将综合介绍目前已知的噬菌体组及其与免疫系统的相互作用。我们首先回顾了噬菌体如何通过细菌表达噬菌体编码的蛋白质间接影响免疫系统。接下来，我们回顾了噬菌体如何直接影响先天性免疫和细菌清除。最后，我们讨论了针对噬菌体的适应性免疫及其对噬菌体/细菌相互作用的影响。根据这些数据，我们提出，我们的微生物组可以理解为一个由细菌、噬菌体和人体细胞组成的相互关联的网络，这些三界相互作用的稳定性可能对维持我们的免疫和代谢健康非常重要。相反，通过接触外源噬菌体、微生物菌群失调或免疫调节失调而破坏这种平衡可能会导致疾病。
Keywords 关键词
bacteriophage, phageome, commensal, immune, phage display, microbiome
噬菌体、噬菌体组、共生体、免疫、噬菌体展示、微生物组
INTRODUCTION 引言
Our microbiome—the aggregate populations of bacteria, viruses, and fungi within our bodies—has major well-established effects on immune development, homeostasis, and function. In turn, the immune system shapes the composition and abundance of those microbial communities (Figure 1).
我们体内的微生物群–细菌、病毒和真菌的集合体–对免疫系统的发育、稳态和功能有着公认的重大影响。反过来，免疫系统也会影响这些微生物群落的组成和丰度（图 1）。
Despite extensive explorations of other components of the microbiome, the human phageome—our endogenous bacteriophages—remains a scientific frontier. The phageome has yet to be characterized for many organs and disease states. Direct interactions between phages and human immune responses are just beginning to be systematically investigated.
尽管对微生物组的其他成分进行了广泛的探索，但人类噬菌体组–我们的内源性噬菌体–仍然是一个科学前沿。许多器官和疾病状态下的噬菌体组尚待鉴定。噬菌体与人体免疫反应之间的直接相互作用刚刚开始得到系统研究。
At present, much of what we know about phages and the immune system comes from studies of phage therapy—the therapeutic use of lytic phages to treat pathogenic bacterial infections—and from work with engineered phages developed for biotechnology applications, including epitope identification, antibody development, and phage vaccines. These are exciting and dynamic fields, as captured by several excellent recent reviews of phage therapy (1, 2) and phage vaccines (3). However, those technologies and therapeutic applications are not the focus of this work.
目前，我们对噬菌体和免疫系统的了解大多来自对噬菌体疗法的研究–利用溶菌噬菌体治疗病原菌感染–以及为生物技术应用而开发的工程噬菌体，包括表位识别、抗体开发和噬菌体疫苗。正如最近几篇关于噬菌体疗法（1, 2）和噬菌体疫苗（3）的精彩综述所反映的那样，这些都是令人兴奋和充满活力的领域。不过，这些技术和治疗应用并不是本研究的重点。
Instead, we review here the burgeoning study of our endogenous phages and their interactions with the mammalian immune system. We propose that bacteriophages are an integral part of our relationships with bacteria and that tri-kingdom interactions between bacteria, bacteriophages, and the human immune system play important roles in health and disease.
相反，我们在此回顾了对内源性噬菌体及其与哺乳动物免疫系统相互作用的新兴研究。我们认为，噬菌体是人类与细菌关系中不可或缺的一部分，细菌、噬菌体和人类免疫系统之间的三界互动在健康和疾病中发挥着重要作用。