| First Author | Palma C | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 2 | Pages | 300-318.e12 |
| PubMed ID | 33421383 | Mgi Jnum | J:303726 |
| Mgi Id | MGI:6510393 | Doi | 10.1016/j.cmet.2020.12.016 |
| Citation | Palma C, et al. (2021) Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis. Cell Metab 33(2):300-318.e12 |
| abstractText | 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. |
