Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> 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 immu...

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Autores principales:	Lanbo Shi, Qingkui Jiang, Yuri Bushkin, Selvakumar Subbian, Sanjay Tyagi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	immunometabolism arachidonic acid metabolism arginine metabolism bioactive lipids glycolysis host-directed therapy Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7656e054cd27456dbf81e74fb6058250
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spelling	oai:doaj.org-article:7656e054cd27456dbf81e74fb60582502021-11-15T15:55:26ZBiphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection10.1128/mBio.02550-182150-7511https://doaj.org/article/7656e054cd27456dbf81e74fb60582502019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02550-18https://doaj.org/toc/2150-7511ABSTRACT 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.Lanbo ShiQingkui JiangYuri BushkinSelvakumar SubbianSanjay TyagiAmerican Society for Microbiologyarticleimmunometabolismarachidonic acid metabolismarginine metabolismbioactive lipidsglycolysishost-directed therapyMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunometabolism arachidonic acid metabolism arginine metabolism bioactive lipids glycolysis host-directed therapy Microbiology QR1-502
spellingShingle	immunometabolism arachidonic acid metabolism arginine metabolism bioactive lipids glycolysis host-directed therapy Microbiology QR1-502 Lanbo Shi Qingkui Jiang Yuri Bushkin Selvakumar Subbian Sanjay Tyagi Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
description	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.
format	article
author	Lanbo Shi Qingkui Jiang Yuri Bushkin Selvakumar Subbian Sanjay Tyagi
author_facet	Lanbo Shi Qingkui Jiang Yuri Bushkin Selvakumar Subbian Sanjay Tyagi
author_sort	Lanbo Shi
title	Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
title_short	Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
title_full	Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
title_fullStr	Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
title_full_unstemmed	Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection
title_sort	biphasic dynamics of macrophage immunometabolism during <italic toggle="yes">mycobacterium tuberculosis</italic> infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/7656e054cd27456dbf81e74fb6058250
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Biphasic Dynamics of Macrophage Immunometabolism during <italic toggle="yes">Mycobacterium tuberculosis</italic> Infection

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