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. © 2020 Elsevier Inc. Through an in vivo model of high susceptibility to MTB infection in DBA/2 mice, we utilized a multi-omic approach to show that caloric restriction (CR) is able to control pulmonary MTB infection and associated inflammatory damage through an immunometabolic reprogramming and enhanced anti-MTB capacity of immune cells. These data candidate CR as a novel strategy in the management of MTB infection in countries where TB is rapidly increasing in association with over-nutrition and obesity.

Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis / C. Palma, C. La Rocca, V. Gigantino, G. Aquino, G. Piccaro, D. Di Silvestre, F. Brambilla, R. Rossi, F. Bonacina, M.T. Lepore, M. Audano, N. Mitro, G. Botti, S. Bruzzaniti, C. Fusco, C. Procaccini, V. De Rosa, M. Galgani, C. Alviggi, A. Puca, F. Grassi, T. Rezzonico-Jost, G.D. Norata, P. Mauri, M.G. Netea, P. de Candia, G. Matarese. - In: CELL METABOLISM. - ISSN 1550-4131. - 33:2(2021 Feb 02), pp. 300-318. [10.1016/j.cmet.2020.12.016]

Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

Bonacina F.;Audano M.;Mitro N.;Norata G. D.;
2021-02-02

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. © 2020 Elsevier Inc. Through an in vivo model of high susceptibility to MTB infection in DBA/2 mice, we utilized a multi-omic approach to show that caloric restriction (CR) is able to control pulmonary MTB infection and associated inflammatory damage through an immunometabolic reprogramming and enhanced anti-MTB capacity of immune cells. These data candidate CR as a novel strategy in the management of MTB infection in countries where TB is rapidly increasing in association with over-nutrition and obesity.
adipose tissue; body weight; caloric restriction; immune response; immunometabolism; infection; T cells; tuberculosis
Settore BIO/14 - Farmacologia
CELL METABOLISM
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/814105
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