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。
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
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.