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      Lipid droplets and the host–pathogen dynamic: FATal attraction?

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          Abstract

          Bosch et al. discuss the role of lipid droplets as a front-line defense in the immune system.

          Abstract

          In the ongoing conflict between eukaryotic cells and pathogens, lipid droplets (LDs) emerge as a choke point in the battle for nutrients. While many pathogens seek the lipids stored in LDs to fuel an expensive lifestyle, innate immunity rewires lipid metabolism and weaponizes LDs to defend cells and animals. Viruses, bacteria, and parasites directly and remotely manipulate LDs to obtain substrates for metabolic energy, replication compartments, assembly platforms, membrane blocks, and tools for host colonization and/or evasion such as anti-inflammatory mediators, lipoviroparticles, and even exosomes. Host LDs counterattack such advances by synthesizing bioactive lipids and toxic nucleotides, organizing immune signaling platforms, and recruiting a plethora of antimicrobial proteins to provide a front-line defense against the invader. Here, we review the current state of this conflict. We will discuss why, when, and how LDs efficiently coordinate and precisely execute a plethora of immune defenses. In the age of antimicrobial resistance and viral pandemics, understanding innate immune strategies developed by eukaryotic cells to fight and defeat dangerous microorganisms may inform future anti-infective strategies.

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          Most cited references190

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          Neutrophil extracellular traps kill bacteria.

          Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
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            Interferon-stimulated genes: a complex web of host defenses.

            Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, we describe ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the JAK-STAT pathway. Several ISGs that directly inhibit virus infection are described with an emphasis on those that impact early and late stages of the virus life cycle. Finally, we describe ongoing efforts to identify and characterize antiviral ISGs, and we provide a forward-looking perspective on the ISG landscape.
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              Dynamics and functions of lipid droplets

              Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.
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                Author and article information

                Journal
                J Cell Biol
                J Cell Biol
                jcb
                The Journal of Cell Biology
                Rockefeller University Press
                0021-9525
                1540-8140
                02 August 2021
                24 June 2021
                : 220
                : 8
                : e202104005
                Affiliations
                [1 ] Lipid Trafficking and Disease Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
                [2 ] Department of Biomedical Sciences, Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain
                [3 ] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
                [4 ] Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
                [5 ] Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia
                [6 ] Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Australia
                [7 ] Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain
                Author notes
                Correspondence to Albert Pol: apols@ 123456ub.edu
                Author information
                https://orcid.org/0000-0002-0406-8139
                https://orcid.org/0000-0002-7494-5248
                https://orcid.org/0000-0002-1750-1085
                Article
                jcb.202104005
                10.1083/jcb.202104005
                8240858
                34165498
                35cbbf04-6c0d-484a-b5d0-ab0b3bb11c48
                © 2021 Bosch et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                : 01 April 2021
                : 02 June 2021
                : 03 June 2021
                Page count
                Pages: 17
                Funding
                Funded by: Fundació la Marató de TV3, DOI http://dx.doi.org/10.13039/100008666;
                Award ID: 31/U/2016
                Funded by: National Health and Medical Research Council, DOI http://dx.doi.org/10.13039/501100000925;
                Award ID: APP1194406
                Funded by: Human Frontier Science Program, DOI http://dx.doi.org/10.13039/501100000854;
                Award ID: RGP0020/2015
                Funded by: Ministerio de Ciencia e Innovación, DOI http://dx.doi.org/10.13039/501100004837;
                Award ID: RTI2018-098593-B-I00
                Funded by: Fundació la Marató de TV3, DOI http://dx.doi.org/10.13039/100008666;
                Award ID: 31/U/2016
                Funded by: CERCA Programme;
                Funded by: Generalitat de Catalunya, DOI http://dx.doi.org/10.13039/501100002809;
                Funded by: National Health and Medical Research Council, DOI http://dx.doi.org/10.13039/501100000925;
                Award ID: APP1037320
                Award ID: 569452
                Funded by: Australian Research Council, DOI http://dx.doi.org/10.13039/501100000923;
                Funded by: Centre of Excellence in Convergent Bio-Nanoscience and Technology;
                Award ID: CE140100036
                Categories
                Review
                Metabolism
                Membrane and Lipid Biology
                Immunology
                Cell Metabolism

                Cell biology
                Cell biology

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