Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

Palma, Carla; Rocca, Claudia La; Gigantino, Vincenzo; Aquino, Gabriella; Piccaro, Giovanni; Silvestre, Dario Di; Brambilla, Francesca; Rossi, Rossana; Bonacina, Fabrizia; Lepore, Maria Teresa; Audano, Matteo; Mitro, Nico; Botti, Gerardo; Bruzzaniti, Sara; Fusco, Clorinda; Procaccini, Claudio; Rosa, Veronica De; Galgani, Mario; Alviggi, Carlo; Puca, Annibale Alessandro; Grassi, Fabio; Rezzonico-Jost, Tanja; Norata, Giuseppe Danilo; Mauri, Pierluigi; Netea, Mihai G.; Candia, Paola de; Matarese, Giuseppe

doi:10.1016/j.cmet.2020.12.016

Cited by 38 publications

(33 citation statements)

References 106 publications

(123 reference statements)

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“…S2 e). Overall, our data provide further indications that host iron metabolism is interconnected to Mtb pathophysiology, and reinforce previous indications that immunometabolic reprogramming is integral to tuberculosis host defense and needs to be more effectively integrated with our therapeutic strategies (Palma et al, 2021;Phelan et al, 2018).…”

Section: Diverging Heme-iron Responses Are Associated With Different Bacterial Phenotypes In Infected Im Subsetssupporting

confidence: 86%

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

Pisu

Huang

Narang

et al. 2021

Journal of Experimental Medicine

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In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis–infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection.

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Section: Diverging Heme-iron Responses Are Associated With Different Bacterial Phenotypes In Infected Im Subsetssupporting

confidence: 86%

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

Pisu

Huang

Narang

et al. 2021

Journal of Experimental Medicine

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“…Targeting immunometabolism as an anti-inflammatory strategy has become an established method in clinical therapies (250,434,435). Recently, Palma et al (436) reported on caloric restriction in mice promoting elimination of Mtb. By means of a multi-omic approach they defined changes in glycolysis next to reduction in fatty acid metabolism and mTOR activity as crucial effects of metabolic reprogramming in this condition (436).…”

Section: Tregs In the Advent Of The Era Of Immunometabolomicsmentioning

confidence: 99%

“…Recently, Palma et al (436) reported on caloric restriction in mice promoting elimination of Mtb. By means of a multi-omic approach they defined changes in glycolysis next to reduction in fatty acid metabolism and mTOR activity as crucial effects of metabolic reprogramming in this condition (436). In addition to anti-inflammatory therapy, these findings on the metabolic properties of Tregs could also be used in tumor therapy to improve anti-tumor immunity via metabolic interventions.…”

Section: Tregs In the Advent Of The Era Of Immunometabolomicsmentioning

confidence: 99%

Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells

et al. 2021

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Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and peripherally induced Tregs remain the most important subpopulations. In multiple sclerosis, a prototypical autoimmune disorder of the central nervous system, Treg dysfunction is a pathogenic hallmark. In contrast, induction of Treg proliferation and enhancement of their function are central immune evasion mechanisms of infectious pathogens. In accordance, Treg expansion is compartmentalized to tissues with high viral replication and prolonged in chronic infections. In friend retrovirus infection, Treg expansion is mainly based on excessive interleukin-2 production by infected effector T cells. Moreover, pathogens seem also to enhance Treg functions as shown in human immunodeficiency virus infection, where Tregs express higher levels of effector molecules such as cytotoxic T-lymphocyte-associated protein 4, CD39 and cAMP and show increased suppressive capacity. Thus, insights into the molecular mechanisms by which intracellular pathogens alter Treg functions might aid to find new therapeutic approaches to target central nervous system autoimmunity. In this review, we summarize the current knowledge of the role of pathogens for Treg function in the context of autoimmune neuroinflammation. We discuss the mechanistic implications for future therapies and provide an outlook for new research directions.

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“…In addition, IL-10/STAT3 axis primed FC differentiation during MTb infection, favoring pathogen persistence (59). Palma et al have shown that controlled caloric restriction protected murine model against pulmonary MTb infection by decreasing bacterial load and FC proliferation to reduce lung damage and limit MTb spreading (60). Thus, the reduction of LDs in MTb-infected FCs might restrain the endocellular survival of MTb (61).…”

Section: Fcs In Mycobacteriosismentioning

confidence: 99%

Progress of the Art of Macrophage Polarization and Different Subtypes in Mycobacterial Infection

Jiang

Xiong

et al. 2021

Front. Immunol.

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Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

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Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

Cited by 38 publications

References 106 publications

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells

Progress of the Art of Macrophage Polarization and Different Subtypes in Mycobacterial Infection

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