Origin and Consequences of Necroinflammation DOI Open Access
Maysa Sarhan, W. Land, Wulf Tonnus

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(2), P. 727 - 780

Published: Feb. 21, 2018

When cells undergo necrotic cell death in either physiological or pathophysiological settings vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium thereby represent strongest known trigger of immune system. With our increasing understanding necrosis as a regulated genetically determined process (RN, necrosis), necroinflammation can be pharmacologically prevented. This review discusses current knowledge about signaling pathways origin necroinflammation. Multiple RN such necroptosis, ferroptosis, pyroptosis have been evolutionary conserved most likely because their differences immunogenicity. As consequence necrosis, however, all damage associated molecular patterns (DAMPs) that extensively investigated over last two decades. Analysis allows characterizing specific signatures for each particular pathway death. While RN-pathways share DAMPs general, them actively regulate system by additional expression and/or maturation pro- anti-inflammatory cytokines/chemokines. In addition, demonstrated to modulate regeneration. For purpose better necroinflammation, we introduce novel classification this help detect relative contribution RN-pathway certain conditions.

Language: Английский

Toll-like Receptors and the Control of Immunity DOI Creative Commons
Katherine A. Fitzgerald, Jonathan C. Kagan

Cell, Journal Year: 2020, Volume and Issue: 180(6), P. 1044 - 1066

Published: March 1, 2020

Language: Английский

Citations

1618
Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation DOI Open Access
Vinícius Fernandes Cruzat, Marcelo Macedo Rogero, Kevin N. Keane

et al.

Nutrients, Journal Year: 2018, Volume and Issue: 10(11), P. 1564 - 1564

Published: Oct. 23, 2018

Glutamine is the most abundant and versatile amino acid in body. In health disease, rate of glutamine consumption by immune cells similar or greater than glucose. For instance, vitro vivo studies have determined that an essential nutrient for lymphocyte proliferation cytokine production, macrophage phagocytic plus secretory activities, neutrophil bacterial killing. release to circulation availability mainly controlled key metabolic organs, such as gut, liver, skeletal muscles. During catabolic/hypercatabolic situations can become function, but its may be compromised due impairment homeostasis inter-tissue metabolism acids. this reason, currently part clinical nutrition supplementation protocols and/or recommended suppressed individuals. However, a wide range (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it difficult determine whether (oral/enteral parenteral) should based on plasma/bloodstream concentration (also known glutaminemia). Although beneficial immune-based effects are already established, many questions evidence positive outcomes still remain presented. Therefore, paper provides integrated review how organs important system. We also discuss action, issues related catabolic situations.

Language: Английский

Citations

890
Macrophages in immunoregulation and therapeutics DOI Creative Commons
Shanze Chen, Abdullah F. U. H. Saeed, Quan Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Language: Английский

Citations

807
Characterization of the Inflammatory Response to Severe COVID-19 Illness DOI Creative Commons
Oliver J. McElvaney, Natalie McEvoy,

Oisín F. McElvaney

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2020, Volume and Issue: 202(6), P. 812 - 821

Published: June 25, 2020

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and identify evidence immunometabolic alterations in those with severe illness.Methods: Levels IL-1β, IL-6, IL-8, IL-10, sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed plasma from healthy volunteers, hospitalized but stable patients (COVIDstable patients), requiring ICU admission (COVIDICU community-acquired pneumonia support (CAPICU patients). Immunometabolic markers measured circulating neutrophils COVID-19. The acute phase response AAT (alpha-1 antitrypsin) was also evaluated.Measurements Main Results: all increased COVIDICU could be clearly differentiated COVIDstable patients, demonstrated higher levels lower IL-10 than CAPICU patients. displayed altered immunometabolism, cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), lactate. production sialylation COVID-19, this antiinflammatory overwhelmed illness, IL-6:AAT ratio markedly (P < 0.0001). In critically unwell increases predicted prolonged stay mortality, whereas improvement associated clinical resolution 0.0001).Conclusions: cytokinemia distinct that other types pneumonia, leading organ failure need. Neutrophils undergo reprogramming illness. Cytokine ratios may predict outcomes population.

Language: Английский

Citations

606
Regulation of immunity and inflammation by hypoxia in immunological niches DOI
Cormac T. Taylor, Sean P. Colgan

Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 17(12), P. 774 - 785

Published: Oct. 3, 2017

Language: Английский

Citations

545
The Role of HIF in Immunity and Inflammation DOI Creative Commons
Anne F. McGettrick, Luke O'neill

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(4), P. 524 - 536

Published: Aug. 26, 2020

Language: Английский

Citations

512
A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation DOI Creative Commons
Niamh C. Williams, Luke O'neill

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Feb. 5, 2018

Metabolism in immune cells is no longer thought of as merely a process for ATP production, biosynthesis and catabolism. The reprogramming metabolic pathways upon activation also the production metabolites that can act signalling molecules. Activated dendritic (DCs) macrophages have an altered Krebs cycle, one consequence which accumulation both citrate succinate. Citrate exported from mitochondria via mitochondrial carrier. Cytosolic metabolism to acetyl-coenzyme A (acetyl-CoA) important fatty-acid synthesis protein acetylation, been linked macrophage DC activation. Citrate-derived itaconate has direct antibacterial effect shown anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify metabolite effector function.

Language: Английский

Citations

482
Regulation of macrophage immunometabolism in atherosclerosis DOI
Graeme J. Koelwyn,

Emma M. Corr,

Ebru Erbay

et al.

Nature Immunology, Journal Year: 2018, Volume and Issue: 19(6), P. 526 - 537

Published: May 17, 2018

Language: Английский

Citations

453
Krebs Cycle Reborn in Macrophage Immunometabolism DOI Open Access
Dylan G. Ryan, Luke O'neill

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 289 - 313

Published: Jan. 27, 2020

A striking change has happened in the field of immunology whereby specific metabolic processes have been shown to be a critical determinant immune cell activation. Multiple receptor types rewire pathways as key part how they promote effector functions. Perhaps surprisingly for immunologists, Krebs cycle emerged central immunometabolic hub macrophage. During proinflammatory macrophage activation, there is an accumulation intermediates succinate and citrate, cycle–derived metabolite itaconate. These metabolites distinct nonmetabolic signaling roles that influence inflammatory gene expression. bioenergetic target cycle, electron transport chain, also becomes altered, generating reactive oxygen species from Complexes I III. Similarly, alternatively activated macrophages require α-ketoglutarate-dependent epigenetic reprogramming elicit anti-inflammatory In this review, we discuss these advances speculate on possibility targeting events therapeutically diseases.

Language: Английский

Citations

331
Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota DOI Creative Commons
Carolina Serena, Victòria Ceperuelo‐Mallafré, Noelia Keiran

et al.

The ISME Journal, Journal Year: 2018, Volume and Issue: 12(7), P. 1642 - 1657

Published: Feb. 6, 2018

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, type 2 diabetes. We aimed to analyze systemic levels of succinate obesity, major risk factor CVD, its relationship with gut microbiome. explored association circulating specific metagenomic signatures cross-sectional prospective cohorts Caucasian Spanish subjects. Obesity was associated elevated concomitant impaired glucose metabolism. This increase changes related metabolism: higher relative abundance succinate-producing Prevotellaceae (P) Veillonellaceae (V), lower succinate-consuming Odoribacteraceae (O) Clostridaceae (C) obese individuals, (P + V/O C) ratio being main determinant plasma succinate. Weight loss intervention decreased coincident reduction In spontaneous evolution after good dietary advice, alterations were linked carbohydrate metabolism energy production independence body weight change. Our data support importance microbe-microbe interactions signature microbiome uncover as microbiota-derived CVD risk.

Language: Английский

Citations

323