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Biphasic Dynamics of Macrophage Immunometabolism during Mycobacterium tuberculosis Infection.

Abstract

Macrophages are the primary targets of Mycobacterium tuberculosis infection; the early events of macrophage interaction with M. tuberculosis define subsequent progression and outcome of infection. M. tuberculosis can alter the innate immunity of macrophages, resulting in suboptimal Th1 immunity, which contributes to the survival, persistence, and eventual dissemination of the pathogen. Recent advances in immunometabolism illuminate the intimate link between the metabolic states of immune cells and their specific functions. In this review, we describe the little-studied biphasic metabolic dynamics of the macrophage response during progression of infection by M. tuberculosis and discuss their relevance to macrophage immunity and M. tuberculosis pathogenicity. The early phase of macrophage infection, which is marked by M1 polarization, is accompanied by a metabolic switch from mitochondrial oxidative phosphorylation to hypoxia-inducible factor 1 alpha (HIF-1α)-mediated aerobic glycolysis (also known as the Warburg effect in cancer cells), as well as by an upregulation of pathways involving oxidative and antioxidative defense responses, arginine metabolism, and synthesis of bioactive lipids. These early metabolic changes are followed by a late adaptation/resolution phase in which macrophages transition from glycolysis to mitochondrial oxidative metabolism, with a consequent dampening of macrophage proinflammatory and antimicrobial responses. Importantly, the identification of upregulated metabolic pathways and/or metabolic regulatory mechanisms with immunomodulatory functions during M1 polarization has revealed novel mechanisms of M. tuberculosis pathogenicity. These advances can lead to the development of novel host-directed therapies to facilitate bacterial clearance in tuberculosis by targeting the metabolic state of immune cells.

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  • Authors+Show Affiliations

    ,

    Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, New Jersey, USA shila@njms.rutgers.edu.

    ,

    Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.

    ,

    Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.

    ,

    Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.

    Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.

    Source

    mBio 10:2 2019 03 26 pg

    MeSH

    Aerobiosis
    Animals
    Glycolysis
    Host-Pathogen Interactions
    Humans
    Macrophages
    Mycobacterium tuberculosis
    Oxidative Phosphorylation
    Tuberculosis

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    30914513

    Citation

    Shi, Lanbo, et al. "Biphasic Dynamics of Macrophage Immunometabolism During Mycobacterium Tuberculosis Infection." MBio, vol. 10, no. 2, 2019.
    Shi L, Jiang Q, Bushkin Y, et al. Biphasic Dynamics of Macrophage Immunometabolism during Mycobacterium tuberculosis Infection. MBio. 2019;10(2).
    Shi, L., Jiang, Q., Bushkin, Y., Subbian, S., & Tyagi, S. (2019). Biphasic Dynamics of Macrophage Immunometabolism during Mycobacterium tuberculosis Infection. MBio, 10(2), doi:10.1128/mBio.02550-18.
    Shi L, et al. Biphasic Dynamics of Macrophage Immunometabolism During Mycobacterium Tuberculosis Infection. MBio. 2019 03 26;10(2) PubMed PMID: 30914513.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Biphasic Dynamics of Macrophage Immunometabolism during Mycobacterium tuberculosis Infection. AU - Shi,Lanbo, AU - Jiang,Qingkui, AU - Bushkin,Yuri, AU - Subbian,Selvakumar, AU - Tyagi,Sanjay, Y1 - 2019/03/26/ PY - 2019/3/28/entrez PY - 2019/3/28/pubmed PY - 2019/5/16/medline KW - arachidonic acid metabolism KW - arginine metabolism KW - bioactive lipids KW - glycolysis KW - host-directed therapy KW - immune response KW - immunometabolism KW - macrophage polarization KW - metabolic modulation KW - redox balancing JF - mBio JO - MBio VL - 10 IS - 2 N2 - Macrophages are the primary targets of Mycobacterium tuberculosis infection; the early events of macrophage interaction with M. tuberculosis define subsequent progression and outcome of infection. M. tuberculosis can alter the innate immunity of macrophages, resulting in suboptimal Th1 immunity, which contributes to the survival, persistence, and eventual dissemination of the pathogen. Recent advances in immunometabolism illuminate the intimate link between the metabolic states of immune cells and their specific functions. In this review, we describe the little-studied biphasic metabolic dynamics of the macrophage response during progression of infection by M. tuberculosis and discuss their relevance to macrophage immunity and M. tuberculosis pathogenicity. The early phase of macrophage infection, which is marked by M1 polarization, is accompanied by a metabolic switch from mitochondrial oxidative phosphorylation to hypoxia-inducible factor 1 alpha (HIF-1α)-mediated aerobic glycolysis (also known as the Warburg effect in cancer cells), as well as by an upregulation of pathways involving oxidative and antioxidative defense responses, arginine metabolism, and synthesis of bioactive lipids. These early metabolic changes are followed by a late adaptation/resolution phase in which macrophages transition from glycolysis to mitochondrial oxidative metabolism, with a consequent dampening of macrophage proinflammatory and antimicrobial responses. Importantly, the identification of upregulated metabolic pathways and/or metabolic regulatory mechanisms with immunomodulatory functions during M1 polarization has revealed novel mechanisms of M. tuberculosis pathogenicity. These advances can lead to the development of novel host-directed therapies to facilitate bacterial clearance in tuberculosis by targeting the metabolic state of immune cells. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/30914513/Biphasic_Dynamics_of_Macrophage_Immunometabolism_during_Mycobacterium_tuberculosis_Infection L2 - http://mbio.asm.org/cgi/pmidlookup?view=long&pmid=30914513 DB - PRIME DP - Unbound Medicine ER -