scholarly journals Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

Science ◽  
2020 ◽  
Vol 370 (6514) ◽  
pp. eaay8085 ◽  
Author(s):  
Marta Bosch ◽  
Miguel Sánchez-Álvarez ◽  
Alba Fajardo ◽  
Ronan Kapetanovic ◽  
Bernhard Steiner ◽  
...  
Keyword(s):  
Host Defense ◽  
Lipid Droplets ◽  
Acid Metabolism ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Eukaryotic Cells ◽  
Metabolic Adaptation ◽  
Intracellular Pathogens ◽  
Defense Proteins ◽  
Danger Signals

Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.

scholarly journals Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella

2010 ◽  
Vol 207 (8) ◽  
pp. 1745-1755 ◽  
Author(s):  
Petr Broz ◽  
Kim Newton ◽  
Mohamed Lamkanfi ◽  
Sanjeev Mariathasan ◽  
Vishva M. Dixit ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Host Defense ◽  
Immune Defense ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Intracellular Pathogens ◽  
Danger Signals ◽  
Caspase 1 ◽  
Innate Immune Defense

Intracellular pathogens and endogenous danger signals in the cytosol engage NOD-like receptors (NLRs), which assemble inflammasome complexes to activate caspase-1 and promote the release of proinflammatory cytokines IL-1β and IL-18. However, the NLRs that respond to microbial pathogens in vivo are poorly defined. We show that the NLRs NLRP3 and NLRC4 both activate caspase-1 in response to Salmonella typhimurium. Responding to distinct bacterial triggers, NLRP3 and NLRC4 recruited ASC and caspase-1 into a single cytoplasmic focus, which served as the site of pro–IL-1β processing. Consistent with an important role for both NLRP3 and NLRC4 in innate immune defense against S. typhimurium, mice lacking both NLRs were markedly more susceptible to infection. These results reveal unexpected redundancy among NLRs in host defense against intracellular pathogens in vivo.

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

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Marta Bosch ◽  
Matthew J. Sweet ◽  
Robert G. Parton ◽  
Albert Pol
Keyword(s):  
Innate Immunity ◽  
Lipid Droplets ◽  
Innate Immune ◽  
Metabolic Energy ◽  
Eukaryotic Cells ◽  
Bioactive Lipids ◽  
Front Line ◽  
Antimicrobial Proteins ◽  
Current State ◽  
Fatal Attraction

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.

Bright Near-Infrared α-TetraphenyletheneBODIPY Nanoprobes with High Aggregated State Emission Quantum Yields in Aqueous System for Lipid Droplet-Specific Imaging

2021 ◽  
Author(s):  
Xing Guo ◽  
Bing Tang ◽  
Hao Wu ◽  
Qing-Hua Wu ◽  
Zeyu Xie ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Host Defense ◽  
Near Infrared ◽  
Cell Metabolism ◽  
Aqueous System ◽  
Innate Immune ◽  
Quantum Yields ◽  
First Responder

Lipid droplet (LD) has been found to be an innate immune first-responder integrating cell metabolism and host defense. The abnormal changes of LD has been believed to be highly associated...

scholarly journals Mycobacterium tuberculosis evasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system

2020 ◽  
Author(s):  
Andrew J. Olive ◽  
Clare M. Smith ◽  
Christina E. Baer ◽  
Jörn Coers ◽  
Christopher M. Sassetti
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Host Defense ◽  
Genetic Interaction ◽  
Mycobacterial Infection ◽  
Secretion System ◽  
Immune Defense ◽  
Chromosome 3 ◽  
Intracellular Pathogens ◽  
Potent Inducer ◽  
Defense Proteins

AbstractCell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown to directly restrict Mycobacterium bovis BCG yet their role during Mtb infection has remained unknown. Here, we examine the importance of a cluster of five GBPs on mouse chromosome 3 in controlling Mycobacterial infection. While M. bovis BCG is directly restricted by GBPs, we find that the GBPs on chromosome 3 do not contribute to the control of Mtb replication or the associated host response to infection. The differential effects of GBPs during Mtb versus M. bovis BCG infection is at least partially explained by the absence of the ESX1 secretion system from M. bovis BCG, since Mtb mutants lacking the ESX1 secretion system become similarly susceptible to GBP-mediated immune defense. Therefore, this specific genetic interaction between the murine host and Mycobacteria reveals a novel function for the ESX1 virulence system in the evasion of GBP-mediated immunity.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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