Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

Cell Metab. 2021 Feb 2;33(2):300-318.e12. doi: 10.1016/j.cmet.2020.12.016. Epub 2021 Jan 8.


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.

Keywords: T cells; adipose tissue; body weight; caloric restriction; immune response; immunometabolism; infection; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caloric Restriction
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / metabolism
  • Tuberculosis / immunology
  • Tuberculosis / metabolism
  • Tuberculosis / prevention & control*