Immunometabolism

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Vijay Kumar - One of the best experts on this subject based on the ideXlab platform.

  • How could we forget Immunometabolism in SARS-CoV2 infection or COVID-19?
    International reviews of immunology, 2020
    Co-Authors: Vijay Kumar
    Abstract:

    SARS-CoV2 infection or COVID-19 has created panic around the world since its first origin in December 2019 in Wuhan city, China. The COVID-19 pandemic has infected more than 46.4 million people, with 1,199,727 deaths. The immune system plays a crucial role in the severity of COVID-19 and the development of pneumonia-induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Along with providing protection, both innate and T cell-based adaptive immune response dysregulate during severe SARS-CoV2 infection. This dysregulation is more pronounced in older population and patients with comorbidities (Diabetes, hypertension, obesity, other pulmonary and autoimmune diseases). However, COVID-19 patients develop protective antibodies (Abs) against SARS-CoV2, but they do not long for last. The induction of the immune response against the pathogen also requires metabolic energy that generates through the process of Immunometabolism. The change in the metabolic stage of immune cells from homeostasis to an inflammatory or infectious environment is called immunometabolic reprogramming. The article describes the cellular immunology (macrophages, T cells, B cells, dendritic cells, NK cells and pulmonary epithelial cells (PEC) and vascular endothelial cells) and the associated immune response during COVID-19. Immunometabolism may serve as a cell-specific therapeutic approach to target COVID-19.

  • how could we forget Immunometabolism in sars cov2 infection or covid 19
    International Reviews of Immunology, 2020
    Co-Authors: Vijay Kumar
    Abstract:

    SARS-CoV2 infection or COVID-19 has created panic around the world since its first origin in December 2019 in Wuhan city, China. The COVID-19 pandemic has infected more than 46.4 million people, with 1,199,727 deaths. The immune system plays a crucial role in the severity of COVID-19 and the development of pneumonia-induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Along with providing protection, both innate and T cell-based adaptive immune response dysregulate during severe SARS-CoV2 infection. This dysregulation is more pronounced in older population and patients with comorbidities (Diabetes, hypertension, obesity, other pulmonary and autoimmune diseases). However, COVID-19 patients develop protective antibodies (Abs) against SARS-CoV2, but they do not long for last. The induction of the immune response against the pathogen also requires metabolic energy that generates through the process of Immunometabolism. The change in the metabolic stage of immune cells from homeostasis to an inflammatory or infectious environment is called immunometabolic reprogramming. The article describes the cellular immunology (macrophages, T cells, B cells, dendritic cells, NK cells and pulmonary epithelial cells (PEC) and vascular endothelial cells) and the associated immune response during COVID-19. Immunometabolism may serve as a cell-specific therapeutic approach to target COVID-19.

  • Immunometabolism: Another Road to Sepsis and Its Therapeutic Targeting
    Inflammation, 2019
    Co-Authors: Vijay Kumar
    Abstract:

    Sepsis is a major health problem all over the world. Despite its existence since the time of Hippocrates (470 BC), sepsis is still a serious medical problem for physicians working in both pediatric and adult intensive care units. The most current US FDA-approved drug called recombinant human activated protein C or Drotrecogin-α is also failed in clinical trials and showed similar effects as placebo. The epidemiological data and studies have indicated sepsis as a major socioeconomic burden all over the world. Advances in immunology and genomic medicine have established different immunological mechanisms as major regulators of the pathogenesis of the sepsis. These immunological mechanisms come into action upon activation of several components of the immune system including innate and adaptive immunity. The activation of these immune cells in response to the pathogens or pathogen-associated molecular patterns (PAMPs) responsible for the onset of sepsis is regulated by the metabolic stage of the immune cells called Immunometabolism. An alternation in the Immunometabolism is responsible for the generation of dysregulated immune response during sepsis and plays a very important role in the process. Thus, it becomes vital to understand the immunometabolic reprograming during sepsis to design future target-based therapeutics depending on the severity. The current review is designed to highlight the importance of immune response and associated Immunometabolism during sepsis and its targeting as a future therapeutic approach.

  • Inflammation research sails through the sea of immunology to reach Immunometabolism.
    International immunopharmacology, 2019
    Co-Authors: Vijay Kumar
    Abstract:

    Inflammation occurs as a result of acute trauma, invasion of the host by different pathogens, pathogen-associated molecular patterns (PAMPs) or chronic cellular stress generating damage-associated molecular patterns (DAMPs). Thus inflammation may occur under both sterile inflammatory conditions including certain cancers, autoimmune or autoinflammatory diseases (Rheumatic arthritis (RA)) and infectious diseases including sepsis, pneumonia-associated acute lung inflammation (ALI) or acute respiratory distress syndrome (ARDS). The pathogenesis of inflammation involves dysregulation of an otherwise protective immune response comprising of various innate and adaptive immune cells and humoral (cytokines and chemokines) mediators secreted by these immune cells upon the activation of signaling mechanisms regulated by the activation of different pattern recognition receptors (PRRs). However, the pro-inflammatory and anti-inflammatory action of these immune cells is determined by the metabolic stage of the immune cells. The metabolic process of immune cells is called Immunometabolism and its shift determined by inflammatory stimuli is called immunometabolic reprogramming. The article focuses on the involvement of various immune cells generating the inflammation, their interaction, immunometabolic reprogramming, and the therapeutic targeting of the Immunometabolism to manage inflammation.

  • T cells and their Immunometabolism: A novel way to understanding sepsis immunopathogenesis and future therapeutics.
    European journal of cell biology, 2018
    Co-Authors: Vijay Kumar
    Abstract:

    Sepsis has always been considered as a big challenge for pharmaceutical companies in terms of discovering and designing new therapeutics. The pathogenesis of sepsis involves aberrant activation of innate immune cells (i.e. macrophages, neutrophils etc.) at early stages. However, a stage of immunosuppression is also observed during sepsis even in the patients who have recovered from it. This stage of immunosuppression is observed due to the loss of conventional (i.e. CD4, CD8) T cells, Th17 cells and an upregulation of regulatory T cells (Tregs). This process also impacts metabolic processes controlling immune cell metabolism called Immunometabolism. The present review is focused on the T cell-mediated immune response, their Immunometabolism and targeting T cell Immunometabolism during sepsis as future therapeutic approach. The first part of the manuscripts describes an impact of sepsis on conventional T cells, Th17 cells and Tregs along with their impact on sepsis. The subsequent section further describes the Immunometabolism of these cells (CD4, CD8, Th17, and Tregs) under normal conditions and during sepsis-induced immunosuppression. The article ends with the therapeutic targeting of T cell Immunometabolism (both conventional T cells and Tregs) during sepsis as a future immunomodulatory approach for its management.

Laurence Morel - One of the best experts on this subject based on the ideXlab platform.

  • Immunometabolism in systemic lupus erythematosus
    Nature Reviews Rheumatology, 2017
    Co-Authors: Laurence Morel
    Abstract:

    Metabolic abnormalities have been reported in immune cells in lupus, notably in T cells from patients with systemic lupus erythematosus (SLE) but also in other immune cell types. This Review discusses recent clinical and experimental evidence for cell-specific metabolic dysfunction in SLE, and the potential therapeutic benefit of targeting these processes. In systemic lupus erythematous (SLE), CD4^+ T cells have a hypermetabolic state dominated by oxidation, mitochondrial abnormalities, activation of mTORC1 and increased glucose flux Targeting T cell metabolism has therapeutic effects in mouse models of lupus and in the T cells of patients with SLE Cell-specific metabolic imbalances probably also affect other immune cells in SLE, including neutrophils, plasma cells and macrophages, and specific metabolic targeting of these cells could have therapeutic benefit A better understanding of the complexities of Immunometabolism in SLE could lead to personalized therapeutic options The metabolome, potentially intersecting with the microbiota, might provide biomarkers for SLE Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4^+ T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4^+ T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.

  • Immunometabolism in systemic lupus erythematosus
    Nature Reviews Rheumatology, 2017
    Co-Authors: Laurence Morel
    Abstract:

    Metabolic abnormalities have been reported in immune cells in lupus, notably in T cells from patients with systemic lupus erythematosus (SLE) but also in other immune cell types. This Review discusses recent clinical and experimental evidence for cell-specific metabolic dysfunction in SLE, and the potential therapeutic benefit of targeting these processes.

Jan Van Den Bossche - One of the best experts on this subject based on the ideXlab platform.

  • Immunometabolism in the Single-Cell Era.
    Cell metabolism, 2020
    Co-Authors: Maxim N Artyomov, Jan Van Den Bossche
    Abstract:

    Summary Emerging research has identified metabolic pathways that are crucial for the proper regulation of immune cells and how, when deranged, they can cause immune dysfunction and disease progression. However, due to technical limitations such insights have relied heavily on bulk measurements in immune cells, often activated in vitro. But with the emergence of single-cell applications, researchers can now estimate the metabolic state of individual immune cells in clinical samples. Here, we review these single-cell techniques and their ability to validate common principles in Immunometabolism, while also revealing context-dependent metabolic heterogeneity within the immune cell compartment. We also discuss current gaps and limitations, as well as identify future opportunities to move the field forward toward the development of therapeutic targets and improved diagnostic capabilities.

  • macrophage Immunometabolism where are we going
    Trends in Immunology, 2017
    Co-Authors: Jan Van Den Bossche, Luke A J Oneill, Deepthi Menon
    Abstract:

    A growing number of findings highlight the crucial role of metabolic reprogramming in macrophage activation. Metabolic pathways are closely interconnected and recent literature demonstrates the need for glucose metabolism in anti-inflammatory as well as inflammatory macrophages. Moreover, fatty acid oxidation (FAO) not only supports anti-inflammatory responses as described formerly but also drives inflammasome activation in inflammatory macrophages. Hence, defining glycolysis as proinflammatory and FAO as anti-inflammatory may be an oversimplification. Here we review how the rapid growth of the Immunometabolism field has improved our understanding of macrophage activation and at the same time has led to an increase in the appearance of contradictory observations. To conclude we discuss current challenges in Immunometabolism and present crucial areas for future research.

  • Macrophage Immunometabolism: Where Are We (Going)?
    Trends in immunology, 2017
    Co-Authors: Jan Van Den Bossche, Luke A. J. O'neill, Deepthi Menon
    Abstract:

    A growing number of findings highlight the crucial role of metabolic reprogramming in macrophage activation. Metabolic pathways are closely interconnected and recent literature demonstrates the need for glucose metabolism in anti-inflammatory as well as inflammatory macrophages. Moreover, fatty acid oxidation (FAO) not only supports anti-inflammatory responses as described formerly but also drives inflammasome activation in inflammatory macrophages. Hence, defining glycolysis as proinflammatory and FAO as anti-inflammatory may be an oversimplification. Here we review how the rapid growth of the Immunometabolism field has improved our understanding of macrophage activation and at the same time has led to an increase in the appearance of contradictory observations. To conclude we discuss current challenges in Immunometabolism and present crucial areas for future research.

Hongbo Chi - One of the best experts on this subject based on the ideXlab platform.

  • Signaling networks in Immunometabolism
    Cell Research, 2020
    Co-Authors: Jordy Saravia, Jana L. Raynor, Nicole M. Chapman, Seon Ah Lim, Hongbo Chi
    Abstract:

    Adaptive immunity is essential for pathogen and tumor eradication, but may also trigger uncontrolled or pathological inflammation. T cell receptor, co-stimulatory and cytokine signals coordinately dictate specific signaling networks that trigger the activation and functional programming of T cells. In addition, cellular metabolism promotes T cell responses and is dynamically regulated through the interplay of serine/threonine kinases, immunological cues and nutrient signaling networks. In this review, we summarize the upstream regulators and signaling effectors of key serine/threonine kinase-mediated signaling networks, including PI3K–AGC kinases, mTOR and LKB1–AMPK pathways that regulate metabolism, especially in T cells. We also provide our perspectives about the pending questions and clinical applicability of immunometabolic signaling. Understanding the regulators and effectors of immunometabolic signaling networks may uncover therapeutic targets to modulate metabolic programming and T cell responses in human disease.

Maxim N Artyomov - One of the best experts on this subject based on the ideXlab platform.

  • Immunometabolism in the Single-Cell Era.
    Cell metabolism, 2020
    Co-Authors: Maxim N Artyomov, Jan Van Den Bossche
    Abstract:

    Summary Emerging research has identified metabolic pathways that are crucial for the proper regulation of immune cells and how, when deranged, they can cause immune dysfunction and disease progression. However, due to technical limitations such insights have relied heavily on bulk measurements in immune cells, often activated in vitro. But with the emergence of single-cell applications, researchers can now estimate the metabolic state of individual immune cells in clinical samples. Here, we review these single-cell techniques and their ability to validate common principles in Immunometabolism, while also revealing context-dependent metabolic heterogeneity within the immune cell compartment. We also discuss current gaps and limitations, as well as identify future opportunities to move the field forward toward the development of therapeutic targets and improved diagnostic capabilities.

  • integrating Immunometabolism and macrophage diversity
    Seminars in Immunology, 2016
    Co-Authors: Maxim N Artyomov, Alexey Sergushichev, Joel D Schilling
    Abstract:

    Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in cellular metabolism are important determinants of macrophage function and phenotype. At the same time, our appreciation of macrophage diversity in vivo has also been increasing. Factors such as cell origin and tissue localization are now recognized as important variables that influence macrophage biology. Whether different macrophage populations also have unique metabolic phenotypes has not been extensively explored. In this article, we will discuss the importance of understanding how macrophage origin can modulate metabolic programming and influence inflammatory responses.