Benler Sean, Koonin Eugene V
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
Bioessays. 2020 Dec;42(12):e2000114. doi: 10.1002/bies.202000114. Epub 2020 Nov 12.
Exploration of immune systems in prokaryotes, such as restriction-modification or CRISPR-Cas, shows that both innate and adaptive systems possess programmed cell death (PCD) potential. The key outstanding question is how the immune systems sense and "predict" infection outcomes to "decide" whether to fight the pathogen or induce PCD. There is a striking parallel between this life-or-death decision faced by the cell and the decision by temperate viruses to protect or kill their hosts, epitomized by the lysis-lysogeny switch of bacteriophage Lambda. Immune systems and temperate phages sense the same molecular inputs, primarily, DNA damage, that determine whether the cell lives or dies. Because temperate (pro)phages are themselves components of prokaryotic genomes, their shared "interests" with the hosts result in coregulation of the lysis-lysogeny switch and immune systems that jointly provide the cell with the decision machinery to probe and predict infection outcomes, answering the life-or-death question.
对原核生物免疫系统的探索，如限制修饰或CRISPR-Cas系统，表明先天和适应性系统都具有程序性细胞死亡（PCD）的潜力。关键的突出问题是免疫系统如何感知并“预测”感染结果，以“决定”是对抗病原体还是诱导PCD。细胞面临的这种生死抉择与温和噬菌体保护或杀死宿主的决定之间存在着惊人的相似之处，噬菌体λ的裂解-溶原开关就是一个典型例子。免疫系统和温和噬菌体感知相同的分子输入，主要是DNA损伤，而这些分子输入决定了细胞的生死。由于温和（原）噬菌体本身就是原核生物基因组的组成部分，它们与宿主的共同“利益”导致裂解-溶原开关和免疫系统的共同调节，共同为细胞提供探测和预测感染结果的决策机制，从而回答生死问题。
