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四环素类抗生素可诱导宿主对疾病的耐受性
2020-10-15 16:23

近日,葡萄牙里斯本大学Luís F. Moita及其团队发现,四环素类抗生素可诱导宿主对疾病的耐受性。相关论文于2020年10月14日在线发表在《免疫》杂志上。

研究人员发现,针对线粒体的四环素类抗生素可预防败血症而不会影响病原体负荷。从机理上讲,研究人员发现蛋白质合成的线粒体抑制会扰动电子传输链(ETC),从而减少肺部组织损伤并增加肝脏中脂肪酸氧化和糖皮质激素的敏感性。使用肝脏特异性的Crif1(蛋白质合成的关键线粒体成分)局部和急性缺失,研究人员发现小鼠受到了败血症的保护,这一现象也可在苯乙双胍对ETC的复合物I的瞬时抑制时出现。
 
因此,研究人员证明靶向线粒体的抗生素不仅具有抗菌活性,而且对线粒体蛋白质合成的抑制(导致ETC扰动)是诱导疾病耐受性的机制。
 
据了解,长期以来,人们已经知道几类抗生素具有益处,而这些作用不能严格根据其控制传染原的能力来解释。
 
附:英文原文

Title: Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection

Author: Henrique G. Colao, André Barros, Ana Neves-Costa, Elsa Seixas, Dora Pedroso, Tiago Velho, Katharina L. Willmann, Pedro Faisca, Gerlinde Grabmann, Hyon-Seung Yi, Minho Shong, Vladimir Benes, Sebastian Weis, Thomas Kcher, Luís F. Moita

Issue&Volume: 2020-10-4

Abstract: Several classes of antibiotics have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here, we report that tetracycline antibiotics, which target the mitoribosome, protected against sepsis without affecting the pathogen load. Mechanistically, we found that mitochondrial inhibition of protein synthesis perturbed the electron transport chain (ETC) decreasing tissue damage in the lung and increasing fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a liver-specific partial and acute deletion of Crif1, a critical mitoribosomal component for protein synthesis, we found that mice were protected against sepsis, an observation that was phenocopied by the transient inhibition of complex I of the ETC by phenformin. Together, we demonstrate that mitoribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a mechanism for the induction of disease tolerance.

DOI: 10.1016/j.immuni.2020.09.011

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30405-2

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx


本期文章:《免疫》:Online/在线发表

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