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      Metabolic strategy of macrophages under homeostasis or immune stress in Drosophila

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          Abstract

          Macrophages are well known for their phagocytic functions in innate immunity across species. In mammals, they rapidly consume a large amount of energy by shifting their metabolism from mitochondrial oxidative phosphorylation toward aerobic glycolysis, to perform the effective bactericidal function upon infection. Meanwhile, they strive for sufficient energy resources by restricting systemic metabolism. In contrast, under nutrient deprivation, the macrophage population is down-regulated to save energy for survival. Drosophila melanogaster possesses a highly conserved and comparatively simple innate immune system. Intriguingly, recent studies have shown that Drosophila plasmatocytes, the macrophage-like blood cells, adopt comparable metabolic remodeling and signaling pathways to achieve energy reassignment when challenged by pathogens, indicating the conservation of such metabolic strategies between insects and mammals. Here, focusing on Drosophila macrophages (plasmatocytes), we review recent advances regarding their comprehensive roles in local or systemic metabolism under homeostasis or stress, emphasizing macrophages as critical players in the crosstalk between the immune system and organic metabolism from a Drosophila perspective.

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          Most cited references118

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          Exploring the full spectrum of macrophage activation.

          Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
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            Macrophage biology in development, homeostasis and disease.

            Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the 'hallmarks' of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.
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              Succinate is an inflammatory signal that induces IL-1β through HIF-1α.

              Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
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                Author and article information

                Contributors
                zhaolong@ouc.edu.cn
                suying@ouc.edu.cn
                Journal
                Mar Life Sci Technol
                Mar Life Sci Technol
                Marine Life Science & Technology
                Springer Nature Singapore (Singapore )
                2096-6490
                2662-1746
                16 August 2022
                16 August 2022
                August 2022
                : 4
                : 3
                : 291-302
                Affiliations
                [1 ]GRID grid.4422.0, ISNI 0000 0001 2152 3263, Institute of Evolution and Marine Biodiversity, , Ocean University of China, ; Qingdao, 266003 China
                [2 ]GRID grid.4422.0, ISNI 0000 0001 2152 3263, College of Marine Life Sciences, , Ocean University of China, ; Qingdao, 266003 China
                [3 ]GRID grid.4422.0, ISNI 0000 0001 2152 3263, Fisheries College, , Ocean University of China, ; Qingdao, 266003 China
                [4 ]GRID grid.419897.a, ISNI 0000 0004 0369 313X, Key Laboratory of Mariculture (OUC), Ministry of Education, ; Qingdao, 266003 China
                Author notes

                Edited by Jiamei Li.

                Article
                134
                10.1007/s42995-022-00134-1
                10077226
                8e06e946-3548-423c-b37a-8637f75bf010
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 February 2022
                : 6 May 2022
                Categories
                Review
                Custom metadata
                © Ocean University of China 2022

                macrophage,drosophila,immune system,metabolism,plasmatocyte
                macrophage, drosophila, immune system, metabolism, plasmatocyte

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