Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

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 PucaFabio Grassi, Tanja Rezzonico-Jost, Giuseppe Danilo Norata, Pierluigi Mauri, Mihai G. Netea, Paola de Candia, Giuseppe Matarese

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish
Pages (from-to)300-318.e12
JournalCell Metabolism
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2 2021

Keywords

  • adipose tissue
  • body weight
  • caloric restriction
  • immune response
  • immunometabolism
  • infection
  • T cells
  • tuberculosis

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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