scholarly journals Metabolic Reprogramming in Immune Response and Tissue Inflammation

2020 ◽  
Vol 40 (9) ◽  
pp. 1990-2001 ◽  
Author(s):  
Lizhe Sun ◽  
Xiaofeng Yang ◽  
Zuyi Yuan ◽  
Hong Wang
Keyword(s):  
Immune Cells ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Molecular Model ◽  
Metabolic Reprogramming ◽  
Epigenetic Therapy ◽  
Atp Production ◽  
Functional Changes ◽  
Adaptive Immune Cells ◽  
Proinflammatory Responses

Innate and adaptive immunity participate in and regulate numerous human diseases. Increasing evidence implies that metabolic reprogramming mediates immune cell functional changes during immune responses. In this review, we present and discuss our current understanding of metabolic regulation in different immune cells and their subsets in response to pathological stimuli. An interactive biochemical and molecular model was established to characterize metabolic reprogramming and their functional implication in anti-inflammatory, immune resolution, and proinflammatory responses. We summarize 2 major features of metabolic reprogramming in inflammatory stages in innate and adaptive immune cells: (1) energy production and biosynthesis reprogramming, including increased glycolysis and decreased oxidative phosphorylation, to secure faster ATP production and biosynthesis for defense response and damage repair and (2) epigenetic reprogramming, including enhanced histone acetylation and suppressed DNA methylation, due to altered accessibility of acetyl/methyl group donor and metabolite-modulated enzymatic activity. Finally, we discuss current strategies of metabolic and epigenetic therapy in cardiovascular disease and recommend cell-specific metabolic and gene-targeted site-specific epigenetic alterations for future therapies.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

The impact of cryopreservation on human peripheral blood leucocyte bioenergetics

2015 ◽  
Vol 128 (10) ◽  
pp. 723-733 ◽  
Author(s):  
Kevin N. Keane ◽  
Emily K. Calton ◽  
Vinicius F. Cruzat ◽  
Mario J. Soares ◽  
Philip Newsholme
Keyword(s):  
Immune Cells ◽  
Human Peripheral Blood ◽  
Coupling Efficiency ◽  
Isolated Cells ◽  
Peripheral Blood Leucocyte ◽  
Atp Production ◽  
Functional Changes ◽  
Glycolytic Activity ◽  
Bioenergetic Analysis ◽  
The Impact

Circulating immune cells are considered a source for biomarkers in health and disease, since they are exposed to nutritional, metabolic and immunological stimuli in the vasculature. Cryopreservation of leucocytes is routinely used for long-term storage and determination of phenotypic/functional changes at a later date. Exploring the role of bioenergetics and mitochondrial (dys)function in leucocytes is often examined by using freshly isolated cells. The aim of the pilot study described herein was to assess leucocyte bioenergetics in cryopreserved cells. Leucocytes were isolated from whole blood, counted and frozen in liquid nitrogen (LN2) for a period of 3 months. Cells were thawed at regular intervals and bioenergetic analysis performed using the Seahorse XFe96 flux analyser. Cryogenic storage reduced cell viability by 20%, but cell bioenergetic responses were largely intact for up to 1 month storage in LN2. However, after 1 month storage, mitochondrial function was impaired as reflected by decreasing basal respiration, ATP production, maximum (MAX) respiration, reserve capacity and coupling efficiency. Conversely, glycolytic activity was increased after 1 month, most notably the enhanced glycolytic response to 25 mM glucose without any change in glycolytic capacity. Finally, calculation of bioenergetic health index (BHI) demonstrated that this potential diagnostic parameter was sensitive to cryopreservation. The present study has demonstrated for the first time that cryopreservation of primary immune cells modified their metabolism in a time-dependent fashion, indicated by attenuated aerobic respiration and enhanced glycolytic activity. Taken together, we recommend caution in the interpretation of bioenergetic responses or BHI in cryopreserved samples.

scholarly journals Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kassem Makki ◽  
Philippe Froguel ◽  
Isabelle Wolowczuk
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune Cells ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Cell Types ◽  
Immune Functions ◽  
Cytokines And Chemokines ◽  
Wide Range

Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field.

scholarly journals Dysregulation of Systemic Immunity in Aging and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Jenny Lutshumba ◽  
Barbara S. Nikolajczyk ◽  
Adam D. Bachstetter
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Subjects ◽  
Brain Inflammation ◽  
Adaptive Immune Cells ◽  
Age Related ◽  
The Brain ◽  
Age Related Changes

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

scholarly journals Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma

2021 ◽  
Vol 10 ◽  
Author(s):  
Shaojie Wu ◽  
Huixian Kuang ◽  
Jin Ke ◽  
Manfei Pi ◽  
Dong-Hua Yang
Keyword(s):  
Multiple Myeloma ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Cell Dysfunction ◽  
Promising Therapeutic Approach ◽  
Tumor Survival

Tumor cells rewire metabolism to meet their increased nutritional demands, allowing the maintenance of tumor survival, proliferation, and expansion. Enhancement of glycolysis and glutaminolysis is identified in most, if not all cancers, including multiple myeloma (MM), which interacts with a hypoxic, acidic, and nutritionally deficient tumor microenvironment (TME). In this review, we discuss the metabolic changes including generation, depletion or accumulation of metabolites and signaling pathways, as well as their relationship with the TME in MM cells. Moreover, we describe the crosstalk among metabolism, TME, and changing function of immune cells during cancer progression. The overlapping metabolic phenotype between MM and immune cells is discussed. In this sense, targeting metabolism of MM cells is a promising therapeutic approach. We propose that it is important to define the metabolic signatures that may regulate the function of immune cells in TME in order to improve the response to immunotherapy.

scholarly journals Total CD3 T Cells Are Necessary and Sufficient to Induce Colitis in Immunodeficient Mice With Dendritic Cell–Specific Deletion of TGFbR2: A Novel IBD Model to Study CD4 and CD8 T-Cell Interaction

2019 ◽  
Vol 26 (2) ◽  
pp. 229-241
Author(s):  
Deepa Rana Jamwal ◽  
Raji V Marati ◽  
Christy A Harrison ◽  
Monica T Midura-Kiela ◽  
Vanessa R Figliuolo Paz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Immunodeficient Mice ◽  
Cell Lineages ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been understudied, largely due to the lack of appropriate models. Methods We previously reported spontaneous colitis in mice with impaired TGFβ signaling due to dendritic cell–specific knockout of TGFbR2 (TGFβR2ΔDC). Here, we demonstrate that crossing TGFβR2ΔDC mice with a Rag1-/- background eliminates all symptoms of colitis and that adoptive transfer of unfractionated CD3+ splenocytes is sufficient to induce progressive colitis in Rag1-/-TGFβR2ΔDC mice. Results Both CD4+ and CD8+ T cells are required for the induction of colitis accompanied by activation of both T-cell lineages and DCs, increased expression of mucosal IFNγ, TNFα, IL6, IL1β, and IL12, and decreased frequencies of CD4+FoxP3+ regulatory T cells. Development of colitis required CD40L expression in CD4+ T cells, and the disease was partially ameliorated by IFNγ neutralization. Conclusions This novel model provides an important tool for studying IBD pathogenesis, in particular the complex interactions among innate and adaptive immune cells in a controlled fashion, and represents a valuable tool for preclinical evaluation of novel therapeutics.

scholarly journals Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chao Cao ◽  
Muming Yu ◽  
Yanfen Chai
Keyword(s):  
Inflammatory Response ◽  
Immune Cells ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Specific Treatment ◽  
Treatment Modalities ◽  
Initial State ◽  
Adaptive Immune Cells ◽  
Secondary Infections

Abstract Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date. Although improved treatment strategies have increased the survival rate during the initial state of excessive inflammatory response, recent trends in sepsis show that mortality occurs at a period of continuous immunosuppressive state in which patients succumb to secondary infections within a few weeks or months due to post-sepsis “immune paralysis.” Immune cell alteration induced by uncontrolled apoptosis has been considered a major cause of significant immunosuppression. Particularly, apoptosis of lymphocytes, including innate immune cells and adaptive immune cells, is associated with a higher risk of secondary infections and poor outcomes. Multiple postmortem studies have confirmed that sepsis-induced immune cell apoptosis occurs in all age groups, including neonates, pediatric, and adult patients, and it is considered to be a primary contributing factor to the immunosuppressive pathophysiology of sepsis. Therapeutic perspectives targeting apoptosis through various strategies could improve survival in sepsis. In this review article, we will focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis will also be discussed.

scholarly journals 67 Immunometabolism – emerging concepts and potential applications in livestock

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 101-101
Author(s):  
Barry J Bradford
Keyword(s):  
Immune System ◽  
Communication Networks ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Whole Body ◽  
Phagocytic Cells ◽  
Adaptive Immune Cells ◽  
Potential Applications ◽  
Host Microbe Interactions

Abstract Our understanding of the immune system emerged from the study of disease processes and the communication networks used by various cell types to respond to pathogens. As with many aspects of physiology, this initial view was colored by the techniques available at the time. With technical advances beginning in the 1990, research in sepsis and obesity began to identify critical interactions between the immune system and metabolism. Our current understanding of these interactions is informed by two active but largely distinct research communities. Many in the field of immunology are utilizing cellular metabolism tools to understand mitochondrial function and fuel use in response to activation of innate and adaptive immune cells, especially as these relate to cancer. From another vantage point, many metabolic physiologists are now seeking to understand the importance of tissue-resident immune cells and immune signaling molecules in metabolic homeostasis and pathologies. Beyond human health implications of recent findings, a number of immunometabolism insights have informed our understanding of livestock health. In inflammatory events, phagocytic cells are activated, and the dramatic increase in oxidative metabolism is driven primarily by glucose use. Metabolism of healthy animals is also influenced by secretions from immune cells. Studies in mice indicate that appropriate host/microbe interactions (balancing protection and tolerance) are mediated by a network of immune cell types in the gut, which is critical to both absorptive and barrier functions of the gut. Adipose tissue immune cells regulate lipolytic rate, insulin sensitivity, and perhaps whole-body inflammatory tone. Local immune cell impacts on metabolism of other organs, including the liver and pancreas, are also emerging. Immunity and metabolism are tightly interwoven, and the evolving understanding of these links may enable nutritional or pharmacological strategies to enhance resilience to disease and alter nutrient partitioning in livestock.

In vitro immunogenicity prediction: bridging between innate and adaptive immunity

Bioanalysis ◽  
2021 ◽  
Author(s):  
Sivan Cohen ◽  
Shan Chung
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
In Vitro Assays ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Clinical Consequences ◽  
Immune Cell Response ◽  
Adaptive Immune Systems

Development of antidrug antibodies (ADAs) is an undesirable potential outcome of administration of biotherapeutics and involves the innate and adaptive immune systems. ADAs can have detrimental clinical consequences: they can reduce biotherapeutic efficacy or produce adverse events. Because animal models are considered poor predictors of immunogenicity in humans, in vitro assays with human innate and adaptive immune cells are commonly used alternatives that can reveal cell-mediated unwanted immune responses. Multiple methods have been developed to assess the immune cell response following exposure to biotherapeutics and estimate the potential immunogenicity of biotherapeutics. This review highlights the role of innate and adaptive immune cells as the drivers of immunogenicity and summarizes the use of these cells in assays to predict clinical ADA.

scholarly journals The Immune Microenvironment of Breast Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1375 ◽  
Author(s):  
Tower ◽  
Ruppert ◽  
Britt
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Early Stage ◽  
Invasive Disease ◽  
Malignant Tumours ◽  
Genetic Changes ◽  
Adaptive Immune Cells ◽  
Response To Chemotherapy

Inflammation is now recognized as a hallmark of cancer. Genetic changes in the cancer cell are accepted as the match that lights the fire, whilst inflammation is seen as the fuel that feeds the fire. Once inside the tumour, the immune cells secrete cytokines that kick-start angiogenesis to ferry in much-needed oxygen and nutrients that encourage the growth of tumours. There is now irrefutable data demonstrating that the immune contexture of breast tumours can influence growth and metastasis. A higher immune cell count in invasive breast cancer predicts prognosis and response to chemotherapy. We are beginning now to define the specific innate and adaptive immune cells present in breast cancer and their role not just in the progression of invasive disease, but also in the development of pre-invasive lesions and their transition to malignant tumours. This review article focusses on the immune cells present in early stage breast cancer and their relationship with the immunoediting process involved in tumour advancement.

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