真核生物能够耐受与其共生的细菌，很重要的原因是其免疫应答激活阈值的精密调控。真核生物通过抑制免疫活性与肠道微生物共存，同时还能对外来致病菌的入侵保持快速、平衡的免疫反应。缺失免疫耐受会破坏宿主与微生物之间的和谐关系而导致炎症。至于真核生物的免疫系统是如何区别对待共生微生物与外来入侵者，目前人们还知之甚少。
在8月14日《细胞—宿主与微生物》（Cell Host & Microbe）的一篇论文中，Lhocine等人通过研究果蝇，发现了一个激活免疫反应的缓冲机制，他们称之为：免疫疾病（Imd）信号的肽聚糖识别蛋白（PGRP-LC）相互作用的抑制器（简称PIMS）。
研究发现，果蝇通过抑制Imd的先天免疫信号来回应其共生细菌。PIMS的表达有IMD（免疫缺陷）依赖性，其基础表达依赖于共生细菌的存在。在没有运用PIMS时，共生细菌会引发抗菌肽基因（AMPs）的组成型表达。此外，当果蝇感染革兰氏阴性细菌时，PIMS突变体能够激活抗菌肽基因进行免疫应答，运用PIMS与肽聚糖识别蛋白（PGRP-LC）的相互作用，消耗质膜肽聚糖识别蛋白，并关闭Imd信号。
该研究表明，共生细菌的免疫耐受性通过建立PIMS，在感染外来细菌时保持Imd信号的平衡。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell Host & Microbe，Vol 4, 147-158, 14 August 2008，Nouara Lhocine, Pascal Meier, and Fran?ois Leulier
PIMS Modulates Immune Tolerance by Negatively Regulating Drosophila Innate Immune Signaling
Nouara Lhocine, Paulo S. Ribeiro, Nicolas Buchon, Alexander Wepf, Rebecca Wilson, Tencho Tenev,Bruno Lemaitre,Matthias Gstaiger, Pascal Meier,and Fran?ois Leulier
Metazoans tolerate commensal-gut microbiota by suppressing immune activation while maintaining the ability to launch rapid and balanced immune reactions to pathogenic bacteria. Little is known about the mechanisms underlying the establishment of this threshold. We report that a recently identified Drosophila immune regulator, which we call PGRP-LC-interacting inhibitor of Imd signaling (PIMS), is required to suppress the Imd innate immune signaling pathway in response to commensal bacteria. pims expression is Imd (immune deficiency) dependent, and its basal expression relies on the presence of commensal flora. In the absence of PIMS, resident bacteria trigger constitutive expression of antimicrobial peptide genes (AMPs). Moreover, pims mutants hyperactivate AMPs upon infection with Gram-negative bacteria. PIMS interacts with the peptidoglycan recognition protein (PGRP-LC), causing its depletion from the plasma membrane and shutdown of Imd signaling. Therefore, PIMS is required to establish immune tolerance to commensal bacteria and to maintain a balanced Imd response following exposure to bacterial infections.
