Cell子刊：热量限制或为结核防治提供新手段 | 热心肠日报
Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis
热量限制促进免疫代谢重组从而预防结核病
10.1016/j.cmet.2020.12.016
01-08, Article
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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-inflammatory response, which concurs with MTB pathogenesis. Herein, we show that controlled caloric restriction (CR), not leading to malnutrition, protects susceptible DBA/2 mice against pulmonary MTB infection by reducing bacterial load, lung immunopathology, and generation of foam cells, an MTB reservoir in lung granulomas. Mechanistically, CR induced a metabolic shift toward glycolysis, and decreased both fatty acid oxidation and mTOR activity associated with induction of autophagy in immune cells. An integrated multi-omics approach revealed a specific CR-induced metabolomic, transcriptomic, and proteomic signature leading to reduced lung damage and protective remodeling of lung interstitial tightness able to limit MTB spreading. Our data propose CR as a feasible immunometabolic manipulation to control MTB infection, and this approach offers an unexpected strategy to boost immunity against MTB.
First Authors:
Carla Palma
Correspondence Authors:
Carla Palma,Giuseppe Matarese
All Authors:
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