Modulation of Macrophage Immunometabolism: A New Approach to Fight Infections

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Янв. 26, 2022

Macrophages are essential innate immune cells that contribute to host defense during infection. An important feature of macrophages is their ability respond extracellular cues and adopt different phenotypes functions in response these stimuli. The evidence accumulated the last decade has highlighted crucial role metabolic reprogramming macrophage activation infectious context. Thus, understanding manipulation immunometabolism infection could be interest develop therapeutic strategies. In this review, we focus on 5 major pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation synthesis, tricarboxylic cycle amino metabolism discuss how they sustain regulate function parasitic, bacterial viral infections as well trained immunity. At end, assess whether some drugs those used clinic development can target for potential therapy with an emphasis SARS-CoV2

Язык: Английский

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Calcium-mediated mitochondrial fission and mitophagy drive glycolysis to facilitate arterivirus proliferation

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012872 - e1012872

Опубликована: Янв. 13, 2025

Mitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival proliferation. Here, we report that infection with swine arterivirus porcine reproductive respiratory syndrome virus (PRRSV), manipulates mitochondria calcium ions (Ca2+) induce mitophagy, thereby reprogramming metabolism facilitate its own replication. Mechanistically, PRRSV-induced is caused by elevated levels Ca2+, derived from endoplasmic reticulum (ER) inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial uniporter (MCU) channels. This process associated increased mitochondria-associated membranes (MAMs), mediated upregulated expression sigma non-opioid intracellular (SIGMAR1). Elevated Ca2+ further activates Ca2+/CaM-dependent protein kinase β (CaMKKβ)-AMP-activated (AMPK)-dynamin-related (DRP1) signaling pathway, which interacts (FIS1) dynamics proteins 49 kDa (MiD49) promote fission. PRRSV infection, alongside fission, triggers mitophagy via PTEN-induced putative (PINK1)-Parkin RBR E3 ubiquitin (Parkin) promoting glycolysis excessive lactate production study reveals mechanism regulates during providing new insights into interplay between host cell metabolism.

Язык: Английский

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Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

PLoS Pathogens, Год журнала: 2019, Номер 15(10), С. e1008057 - e1008057

Опубликована: Окт. 31, 2019

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type VA-type have been reported humans. One limitation towards a better understanding these has lack physiologically relevant cell culture model supports growth all HAstV. Herein, we demonstrate infection HAstV strains belonging to three epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived crypts. A detailed investigation VA1, member non-canonical HAstV-VA/HMO clade, showed robust replication HIE derived different patients regions independent cellular differentiation status. Flow cytometry immunofluorescence analysis revealed VA1 infects several types, including progenitor cells mature enterocytes, cultures. profiling VA1-infected uncovered host response is dominated by interferon (IFN)-mediated innate immune responses. comparison antiviral non-transformed transformed colon carcinoma Caco-2 highlighted significant differences between cells, an increased magnitude HIE. Additional studies confirmed sensitivity exogenous IFNs, indicated endogenous IFN curtail clades. Genotypic variation permissiveness lines could be overcome pharmacologic inhibition JAK/STAT signaling. Collectively, our data identify as universal for improved epithelium investigate enteric virus-host interactions.

Язык: Английский

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Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism

Annual Review of Virology, Год журнала: 2021, Номер 8(1), С. 373 - 391

Опубликована: Сен. 29, 2021

Over the past decades, there have been tremendous efforts to understand cross-talk between viruses and host metabolism. Several studies elucidated mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, nucleotide These are evolutionarily conserved across tree of life extremely important for host's nutrient utilization energy production. In this review, we focus on glutamine, acid metabolism highlight manipulated by different classes increase their replication. We also explore a new system hormones in mimic endocrine system. discuss insulin/IGF-1-like peptides potential effects Together, these pathogenesis targeting cellular signaling create multidimensional network interactions proteins. Defining better understanding will help us develop therapeutic tools prevent treat infections.

Язык: Английский

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Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis

Cell Reports, Год журнала: 2021, Номер 37(5), С. 109911 - 109911

Опубликована: Ноя. 1, 2021

Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ increasing inflammatory cytokines. Adoptive transfer these into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, delayed growth. Mechanistically, αKG leads to an energetic state reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation expression complex enzymes. Furthermore, carbons from ectopic are directly utilized generation fatty acids, associated lipidome remodeling triacylglyceride stores. Notably, inhibition either II or DGAT2-mediated synthesis restores decreases αKG-induced phenotype. Thus, identify crosstalk between αKG, metabolism controls fate.

Язык: Английский

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Glycolytic inhibitor 2-deoxy-d-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions

Life Sciences, Год журнала: 2022, Номер 295, С. 120411 - 120411

Опубликована: Фев. 16, 2022

Язык: Английский

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Virologs, viral mimicry, and virocell metabolism: the expanding scale of cellular functions encoded in the complex genomes of giant viruses

FEMS Microbiology Reviews, Год журнала: 2023, Номер 47(5)

Опубликована: Сен. 1, 2023

The phylum Nucleocytoviricota includes the largest and most complex viruses known. These "giant viruses" have a long evolutionary history that dates back to early diversification of eukaryotes, over time they evolved elaborate strategies for manipulating physiology their hosts during infection. One captivating these mechanisms involves use genes acquired from host-referred here as viral homologs or "virologs"-as means promoting propagation. best-known examples are involved in mimicry, which machinery "imitates" immunomodulatory elements vertebrate defense system. But recent findings highlighted vast rapidly expanding array other virologs include many not typically found viruses, such those translation, central carbon metabolism, cytoskeletal structure, nutrient transport, vesicular trafficking, light harvesting. Unraveling roles infection well pathways through functional repertoires by important frontiers at forefront giant virus research.

Язык: Английский

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Metabolic regulation of type I interferon production

Immunological Reviews, Год журнала: 2024, Номер 323(1), С. 276 - 287

Опубликована: Март 11, 2024

Summary Over the past decade, there has been a surge in discoveries of how metabolic pathways regulate immune cell function health and disease, establishing field immunometabolism. Specifically, such as glycolysis, tricarboxylic acid (TCA) cycle, those involving lipid metabolism have implicated regulating function. Viral infections cause immunometabolic changes which lead to antiviral immunity, but little is known about interferon responses. Interferons are critical cytokines host defense, rapidly induced upon pathogen recognition, also involved autoimmune diseases. This review summarizes change impacts production. We describe (specifically eicosanoids cholesterol), TCA cycle‐linked intermediates itaconate fumarate impact type I interferons. Targeting these presents new therapeutic possibilities modulate interferons during defense or disorders.

Язык: Английский

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Feline Calicivirus Infection Manipulates Central Carbon Metabolism

Veterinary Sciences, Год журнала: 2025, Номер 12(2), С. 138 - 138

Опубликована: Фев. 7, 2025

Viruses can manipulate the host metabolism to achieve optimal replication conditions, and central carbon (CCM) pathways are often crucial in determining viral infections. Feline calicivirus (FCV), a diminutive RNA agent, induces upper respiratory tract infections feline hosts, with highly pathogenic strains capable of precipitating systemic subsequent cell necrosis, thereby presenting formidable challenge survival protection. However, relationship between FCV remains unclear, precise mechanisms yet be elucidated. Upon infection Crandell-Rees Kidney (CRFK) cells, an enhanced cellular uptake glucose glutamine was observed. Metabolomics analyses disclosed pronounced alterations infected cells. found augment glycolytic activity while sustaining tricarboxylic acid (TCA) cycle flux, ATP levels remaining invariant. Concurrently, both flux pentose phosphate pathway (PPP) were noted intensified. The application various inhibitory agents targeting glycolysis, metabolism, PPP resulted significant suppression proliferation. Experiments involving deprivation demonstrated that absence either nutrient markedly curtailed replication. Collectively, these findings suggest critical interplay stimulates CRFK cells uptake, supplying necessary metabolic substrates energy for During infection, emerges as primary substrate, ensuring production homeostasis, is predominantly channeled into facilitate nucleotide synthesis.

Язык: Английский

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Breath analysis for detection of viral infection, the current position of the field

Journal of Breath Research, Год журнала: 2020, Номер 14(4), С. 041001 - 041001

Опубликована: Июнь 12, 2020

The COVID-19 pandemic has highlighted the importance of rapid, cost effective, accurate, and non-invasive testing for viral infections. Volatile compounds (VCs) have been suggested several decades as fulfilling these criteria. However currently very little work done in trying to diagnose infections using VCs. Much carried out date involves differentiation bacterial sources infection often detection co-infection. However, this usually vitro involved use human participants. Viruses hijack host cell metabolism do not produce their own metabolites so identifying virus specific VCs is at best a challenging task. there are proteins lipids that potential candidates markers infection. current understanding glycolysis upregulated under increase available energy replication. There some evidence leads production fatty acids, alkanes, alkanes related products. For instance, 2,3-butandione, aldehydes, 2,8-dimethyl-undecane n-propyl acetate all correlated with Currently, literature points oxidative stress (e.g. nitric oxide, aldehydes etc) being most useful determination issue, however, also many other conditions can lead produced. In review range (mainly mass spectrometric) methods discussed breath, including breath condensate. Currently MALDI-ToF-MS likely be preferred method identification strains variants those strains, however it limited by its need sequenced logged database.

Язык: Английский

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