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.

Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis / Palma, Carla; La Rocca, Claudia; Gigantino, Vincenzo; Aquino, Gabriella; Piccaro, Giovanni; Di Silvestre, Dario; Brambilla, Francesca; Rossi, Rossana; Bonacina, Fabrizia; Lepore, Maria Teresa; Audano, Matteo; Mitro, Nico; Botti, Gerardo; Bruzzaniti, Sara; Fusco, Clorinda; Procaccini, Claudio; De Rosa, Veronica; Galgani, Mario; Alviggi, Carlo; Puca, Annibale; Grassi, Fabio; Rezzonico-Jost, Tanja; Norata, Giuseppe Danilo; Mauri, Pierluigi; Netea, Mihai G; de Candia, Paola; Matarese, Giuseppe. - In: CELL METABOLISM. - ISSN 1550-4131. - 33:2(2021), pp. 300-318.e12. [10.1016/j.cmet.2020.12.016]

Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

La Rocca, Claudia;Lepore, Maria Teresa;Fusco, Clorinda;Procaccini, Claudio;De Rosa, Veronica;Galgani, Mario;Alviggi, Carlo;Grassi, Fabio;Norata, Giuseppe Danilo;de Candia, Paola;Matarese, Giuseppe
2021

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.
2021
Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis / Palma, Carla; La Rocca, Claudia; Gigantino, Vincenzo; Aquino, Gabriella; Piccaro, Giovanni; Di Silvestre, Dario; Brambilla, Francesca; Rossi, Rossana; Bonacina, Fabrizia; Lepore, Maria Teresa; Audano, Matteo; Mitro, Nico; Botti, Gerardo; Bruzzaniti, Sara; Fusco, Clorinda; Procaccini, Claudio; De Rosa, Veronica; Galgani, Mario; Alviggi, Carlo; Puca, Annibale; Grassi, Fabio; Rezzonico-Jost, Tanja; Norata, Giuseppe Danilo; Mauri, Pierluigi; Netea, Mihai G; de Candia, Paola; Matarese, Giuseppe. - In: CELL METABOLISM. - ISSN 1550-4131. - 33:2(2021), pp. 300-318.e12. [10.1016/j.cmet.2020.12.016]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/829714
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