真核生物能夠耐受與其共生的細菌,，很重要的原因是其免疫應(yīng)答激活閾值的精密調(diào)控,。真核生物通過抑制免疫活性與腸道微生物共存,，同時還能對外來致病菌的入侵保持快速、平衡的免疫反應(yīng),。缺失免疫耐受會破壞宿主與微生物之間的和諧關(guān)系而導(dǎo)致炎癥,。至于真核生物的免疫系統(tǒng)是如何區(qū)別對待共生微生物與外來入侵者，目前人們還知之甚少,。
在8月14日《細胞—宿主與微生物》（Cell Host & Microbe）的一篇論文中,，Lhocine等人通過研究果蠅，發(fā)現(xiàn)了一個激活免疫反應(yīng)的緩沖機制,，他們稱之為：免疫疾病（Imd）信號的肽聚糖識別蛋白（PGRP-LC）相互作用的抑制器（簡稱PIMS）,。
研究發(fā)現(xiàn)，果蠅通過抑制Imd的先天免疫信號來回應(yīng)其共生細菌,。PIMS的表達有IMD（免疫缺陷）依賴性,，其基礎(chǔ)表達依賴于共生細菌的存在。在沒有運用PIMS時,，共生細菌會引發(fā)抗菌肽基因（AMPs）的組成型表達,。此外，當(dāng)果蠅感染革蘭氏陰性細菌時,，PIMS突變體能夠激活抗菌肽基因進行免疫應(yīng)答,，運用PIMS與肽聚糖識別蛋白（PGRP-LC）的相互作用,，消耗質(zhì)膜肽聚糖識別蛋白，并關(guān)閉Imd信號,。
該研究表明,，共生細菌的免疫耐受性通過建立PIMS，在感染外來細菌時保持Imd信號的平衡,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
