scholarly journals The Role of Metabolic Enzymes in the Regulation of Inflammation

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 426
Author(s):  
Wesley H. Godfrey ◽  
Michael D. Kornberg
Keyword(s):  
Immune Response ◽  
Metabolic Networks ◽  
Clinical Intervention ◽  
Metabolic Enzymes ◽  
Metabolic Reprogramming ◽  
Effector Functions ◽  
Downstream Effector ◽  
Moonlighting Functions ◽  
External Stimuli

Immune cells undergo dramatic metabolic reprogramming in response to external stimuli. These metabolic pathways, long considered as simple housekeeping functions, are increasingly understood to critically regulate the immune response, determining the activation, differentiation, and downstream effector functions of both lymphoid and myeloid cells. Within the complex metabolic networks associated with immune activation, several enzymes play key roles in regulating inflammation and represent potential therapeutic targets in human disease. In some cases, these enzymes control flux through pathways required to meet specific energetic or metabolic demands of the immune response. In other cases, key enzymes control the concentrations of immunoactive metabolites with direct roles in signaling. Finally, and perhaps most interestingly, several metabolic enzymes have evolved moonlighting functions, with roles in the immune response that are entirely independent of their conventional enzyme activities. Here, we review key metabolic enzymes that critically regulate inflammation, highlighting mechanistic insights and opportunities for clinical intervention.

scholarly journals Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 161 ◽  
Author(s):  
Lonneke V. Nouwen ◽  
Bart Everts
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Amino Acid ◽  
Immune Responses ◽  
Metabolic Pathways ◽  
Immune Escape ◽  
Mammalian Target Of Rapamycin ◽  
Metabolic Reprogramming ◽  
First Line

Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy.

scholarly journals The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Aviad Ben-Shmuel ◽  
Batel Sabag ◽  
Guy Biber ◽  
Mira Barda-Saad
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Signaling Pathways ◽  
Natural Killer ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Cell Immune Response ◽  
Effector Functions ◽  
Health And Disease

Natural killer (NK) cells are innate lymphoid cells, which play key roles in elimination of virally infected and malignant cells. The balance between activating and inhibitory signals derived from NK surface receptors govern the NK cell immune response. The cytoskeleton facilitates most NK cell effector functions, such as motility, infiltration, conjugation with target cells, immunological synapse assembly, and cytotoxicity. Though many studies have characterized signaling pathways that promote actin reorganization in immune cells, it is not completely clear how particular cytoskeletal architectures at the immunological synapse promote effector functions, and how cytoskeletal dynamics impact downstream signaling pathways and activation. Moreover, pioneering studies employing advanced imaging techniques have only begun to uncover the architectural complexity dictating the NK cell activation threshold; it is becoming clear that a distinct organization of the cytoskeleton and signaling receptors at the NK immunological synapse plays a decisive role in activation and tolerance. Here, we review the roles of the actin cytoskeleton in NK cells. We focus on how actin dynamics impact cytolytic granule secretion, NK cell motility, and NK cell infiltration through tissues into inflammatory sites. We will also describe the additional cytoskeletal components, non-muscle Myosin II and microtubules that play pivotal roles in NK cell activity. Furthermore, special emphasis will be placed on the role of the cytoskeleton in assembly of immunological synapses, and how mutations or downregulation of cytoskeletal accessory proteins impact NK cell function in health and disease.

scholarly journals Ironing out Macrophage Immunometabolism

2019 ◽  
Vol 12 (2) ◽  
pp. 94 ◽  
Author(s):  
Stefania Recalcati ◽  
Elena Gammella ◽  
Gaetano Cairo
Keyword(s):  
Iron Metabolism ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Macrophage Activation ◽  
Metabolic Reprogramming ◽  
Iron Availability ◽  
Effector Functions ◽  
Expression Of Genes ◽  
Macrophage Plasticity

Over the last decade, increasing evidence has reinforced the key role of metabolic reprogramming in macrophage activation. In addition to supporting the specific immune response of different subsets of macrophages, intracellular metabolic pathways also directly control the specialized effector functions of immune cells. In this context, iron metabolism has been recognized as an important component of macrophage plasticity. Since macrophages control the availability of this essential metal, changes in the expression of genes coding for the major proteins of iron metabolism may result in different iron availability for the macrophage itself and for other cells in the microenvironment. In this review, we discuss how macrophage iron can also play a role in immunometabolism.

scholarly journals Functional characterization of the cnidarian antiviral immune response reveals ancestral complexity

2020 ◽  
Author(s):  
Magda Lewandowska ◽  
Ton Sharoni ◽  
Yael Admoni ◽  
Reuven Aharoni ◽  
Yehu Moran
Keyword(s):  
Immune Response ◽  
Rna Viruses ◽  
Functional Characterization ◽  
Future Research ◽  
Ancestral State ◽  
Viral Dsrna ◽  
Antiviral Immune Response ◽  
Downstream Effector

ABSTRACTAnimals developed a broad repertoire of innate immune sensors and downstream effector cascades for defense against RNA viruses. Yet, this system highly varies between different bilaterian animals, masking its ancestral state. In this study we aimed to characterize the antiviral immune response of the cnidarian Nematostella vectensis and decipher the function of the retinoic acid-inducible gene I-like receptors (RLRs) known to detect viral double-stranded RNA (dsRNA) in bilaterians, but activate different antiviral pathways in vertebrates and nematodes. We show that a mimic of long viral dsRNA triggers a complex antiviral immune response bearing features distinctive for both vertebrate and invertebrate systems. Furthermore, the results of affinity assays and knockdown experiments provide functional evidence for the conserved role of RLRs in initiating immune response to dsRNA that originated before the cnidarian-bilaterian split and lay a strong foundation for future research on the evolution of the immune responses to RNA viruses.

scholarly journals The role of γδТ- and NK-сells in immune response

2010 ◽  
Vol 9 (5) ◽  
pp. 138-142 ◽  
Author(s):  
Ye. G. Churina ◽  
O. I. Urazova ◽  
V. V. Novitsky ◽  
I. O. Naslednikova ◽  
O. V. Voronkova
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Inhibitory Effect ◽  
Antibacterial Action ◽  
Effector Functions

The article presents up-to-date literature data on the role of γδТ-cells and different NK-cells subpopulations in the immune response. Their origin, immunophenotypes, range of secreted cytokines as well as effector functions and factors having stimulating and inhibitory effect on γδТ- and NK-cells are described. Mechanisms of antibacterial action of this type of cells are analyzed. 

scholarly journals Metabolic differentiation and intercellular nurturing underpin bacterial endospore formation

2021 ◽  
Vol 7 (4) ◽  
pp. eabd6385
Author(s):  
Eammon P. Riley ◽  
Javier Lopez-Garrido ◽  
Joseph Sugie ◽  
Roland B. Liu ◽  
Kit Pogliano
Keyword(s):  
Protein Synthesis ◽  
Bacillus Subtilis ◽  
Small Molecule ◽  
Mother Cell ◽  
Metabolic Enzymes ◽  
Metabolic Reprogramming ◽  
Intercellular Transport ◽  
Intensive Research ◽  
Dormant Spore

Despite intensive research, the role of metabolism in bacterial sporulation remains poorly understood. Here, we demonstrate that Bacillus subtilis sporulation entails a marked metabolic differentiation of the two cells comprising the sporangium: the forespore, which becomes the dormant spore, and the mother cell, which dies as sporulation completes. Our data provide evidence that metabolic precursor biosynthesis becomes restricted to the mother cell and that the forespore becomes reliant on mother cell–derived metabolites for protein synthesis. We further show that arginine is trafficked between the two cells and that proposed proteinaceous channels mediate small-molecule intercellular transport. Thus, sporulation entails the profound metabolic reprogramming of the forespore, which is depleted of key metabolic enzymes and must import metabolites from the mother cell. Together, our results provide a bacterial example analogous to progeny nurturing.

scholarly journals Role of Mast Cells and Type 2 Innate Lymphoid (ILC2) Cells in Lung Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Esmaeil Mortaz ◽  
Saeede Amani ◽  
Sharon Mumby ◽  
Ian M. Adcock ◽  
Mehrnaz Movassaghi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cells ◽  
Lung Transplantation ◽  
Cell Activity ◽  
Adaptive Immune Response ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Alloreactive T Cell ◽  
External Stimuli

The multifunctional role of mast cells (MCs) in the immune system is complex and has not fully been explored. MCs reside in tissues and mucous membranes such as the lung, digestive tract, and skin which are strategically located at interfaces with the external environment. These cells, therefore, will encounter external stimuli and pathogens. MCs modulate both the innate and the adaptive immune response in inflammatory disorders including transplantation. MCs can have pro- and anti-inflammatory functions, thereby regulating the outcome of lung transplantation through secretion of mediators that allow interaction with other cell types, particularly innate lymphoid cells (ILC2). ILC2 cells are a unique population of hematopoietic cells that coordinate the innate immune response against a variety of threats including infection, tissue damage, and homeostatic disruption. In addition, MCs can modulate alloreactive T cell responses or assist in T regulatory (Treg) cell activity. This paper outlines the current understanding of the role of MCs in lung transplantation, with a specific focus on their interaction with ILC2 cells within the engrafted organ.

scholarly journals Murine interstitial nephritis. I. Analysis of disease susceptibility and its relationship of pleiomorphic gene products defining both immune-response genes and a restrictive requirement for cytotoxic T cells at H-2K.

1982 ◽  
Vol 155 (4) ◽  
pp. 1075-1085 ◽  
Author(s):  
E G Neilson ◽  
S M Phillips
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Interstitial Nephritis ◽  
Cytotoxic T Cells ◽  
Gene Products ◽  
Effector Functions ◽  
Immune Response Genes ◽  
Relationship Of ◽  
Cytotoxic Effector

Anti-tubular basement membrance (alpha TBM) disease-producing interstitial nephritis in mice is not dependent on the generation of alpha TBM antibodies. Susceptibility seems to be defined by very private specificities in H-2K. These specificities are pleiomorphic, providing both immune-response genes and identity restrictions for cytotoxic effector functions expressed by a Thy-1.2+, Lyt-2,3+ T cell. These studies establish a role for T cells in the pathogenesis in interstitial nephritis as well as providing further evidence for the role of H-2K in the expression of an autoimmune disease.

scholarly journals Th17 Cells in Viral Infections—Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1159
Author(s):  
Iury Amancio Paiva ◽  
Jéssica Badolato-Corrêa ◽  
Débora Familiar-Macedo ◽  
Luzia Maria de-Oliveira-Pinto
Keyword(s):  
Immune Response ◽  
Th17 Cells ◽  
Viral Infections ◽  
Critical Role ◽  
Virus Infections ◽  
Effector Functions ◽  
Epithelial Barriers ◽  
Bacteria And Fungi ◽  
Pro Inflammatory Cytokines

Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host’s immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

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