小柯机器人

近日，意大利那不勒斯"费德里克二世"大学Giuseppe Matarese、Carla Palma等研究人员合作发现，热量限制可促进免疫代谢重编程来预防结核病。这一研究成果于2021年1月8日在线发表在《细胞—代谢》上。

研究人员发现，控制的热量限制（CR）不会导致营养不良，它通过减少细菌负荷、肺部免疫病理学和泡沫细胞（肺肉芽肿中的结核分枝杆菌储库）的生成，来保护易感的DBA/2小鼠免受肺结核分枝杆菌（MTB）感染。

从机理上讲，CR诱导了代谢向糖酵解的转变，并降低了与免疫细胞中自噬诱导有关的脂肪酸氧化和mTOR活性。集成的多组学方法揭示了特定CR诱导的代谢组学、转录组学和蛋白质组学特征，从而减少了肺损伤，保护了肺间质紧密性，最终限制了MTB的扩散。

这些数据提出CR是控制MTB感染的免疫代谢操纵，并且这种方法提供了增强MTB免疫力的意外策略。

据介绍，代谢状态与MTB感染的易感性之间存在很强的关系，能量代谢为活化的免疫炎症反应奠定了基础，这与MTB的发病机理是一致的。

附：英文原文

Title: Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

Author: Carla Palma, Claudia La Rocca, Vincenzo Gigantino, Gabriella Aquino, Giovanni Piccaro, Dario Di Silvestre, Francesca Brambilla, Rossana Rossi, Fabrizia Bonacina, Maria Teresa Lepore, Matteo Audano, Nico Mitro, Gerardo Botti, Sara Bruzzaniti, Clorinda Fusco, Claudio Procaccini, Veronica De Rosa, Mario Galgani, Carlo Alviggi, Annibale Puca, Fabio Grassi, Tanja Rezzonico-Jost, Giuseppe Danilo Norata, Pierluigi Mauri, Mihai G. Netea, Paola de Candia, Giuseppe Matarese

Issue&Volume: 2021-01-08

Abstract: There is a strong relationship between metabolic state and susceptibility to Mycobacterium tuberculosis (MTB) infection, with energy metabolism setting the basis for an exaggerated immuno-inflammatoryresponse, which concurs with MTB pathogenesis. Herein, we show that controlled caloricrestriction (CR), not leading to malnutrition, protects susceptible DBA/2 mice againstpulmonary MTB infection by reducing bacterial load, lung immunopathology, and generationof foam cells, an MTB reservoir in lung granulomas. Mechanistically, CR induced ametabolic shift toward glycolysis, and decreased both fatty acid oxidation and mTORactivity associated with induction of autophagy in immune cells. An integrated multi-omicsapproach revealed a specific CR-induced metabolomic, transcriptomic, and proteomicsignature leading to reduced lung damage and protective remodeling of lung interstitialtightness able to limit MTB spreading. Our data propose CR as a feasible immunometabolicmanipulation to control MTB infection, and this approach offers an unexpected strategyto boost immunity against MTB.

DOI: 10.1016/j.cmet.2020.12.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30671-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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