scholarly journals Immunosuppressive network promotes immunosenescence associated with aging and chronic inflammatory conditions

2021 ◽  
Author(s):  
Antero Salminen
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Inflammatory Mediators ◽  
Suppressor Cells ◽  
Low Grade ◽  
Mutual Cooperation ◽  
Inflammatory Conditions ◽  
Arginase 1 ◽  
Age Related ◽  
Immunosuppressive Factors

AbstractThe functional competence of the immune system gradually declines with aging, a process called immunosenescence. The age-related remodelling of the immune system affects both adaptive and innate immunity. In particular, a chronic low-grade inflammation, termed inflammaging, is associated with the aging process. Immunosenescence not only is present in inflammaging state, but it also occurs in several pathological conditions in conjunction with chronic inflammation. It is known that persistent inflammation stimulates a counteracting compensatory immunosuppression intended to protect host tissues. Inflammatory mediators enhance myelopoiesis and induce the generation of immature myeloid-derived suppressor cells (MDSC) which in mutual cooperation stimulates the immunosuppressive network. Immunosuppressive cells, especially MDSCs, regulatory T cells (Treg), and M2 macrophages produce immunosuppressive factors, e.g., TGF-β, IL-10, ROS, arginase-1 (ARG1), and indoleamine 2,3-dioxygenase (IDO), which suppress the functions of CD4/CD8T and B cells as well as macrophages, natural killer (NK) cells, and dendritic cells. The immunosuppressive armament (i) inhibits the development and proliferation of immune cells, (ii) decreases the cytotoxic activity of CD8T and NK cells, (iii) prevents antigen presentation and antibody production, and (iv) suppresses responsiveness to inflammatory mediators. These phenotypes are the hallmarks of immunosenescence. Immunosuppressive factors are able to control the chromatin landscape, and thus, it seems that the immunosenescence state is epigenetically regulated.

scholarly journals Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

2016 ◽  
Author(s):  
Tania Rescigno ◽  
Mario F. Tecce ◽  
Anna Capasso
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Aging Process ◽  
Bioactive Molecules ◽  
Low Grade ◽  
Molecular Processes ◽  
Ample Evidence ◽  
Inflammatory Status ◽  
Age Related

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

scholarly journals Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

2016 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  
Keyword(s):  
Immune System ◽  
Murine Model ◽  
Gut Microbiome ◽  
Inflammatory Marker ◽  
Low Grade ◽  
Host Immune System ◽  
Cancer Type ◽  
Microbiome Composition ◽  
Aged Mice ◽  
Age Related

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.

scholarly journals Global immune fingerprinting in glioblastoma reveals immune-suppression signatures associated with prognosis

2018 ◽  
Author(s):  
Tyler J. Alban ◽  
Alvaro G. Alvarado ◽  
Mia D. Sorensen ◽  
Defne Bayik ◽  
Josephine Volovetz ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
Disease Progression ◽  
Poor Prognosis ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Low Grade ◽  
Immune Profile ◽  
Tumor Types ◽  
Extended Survival

Abstract/SummaryGlioblastoma (GBM) remains uniformly lethal, and, despite a large accumulation of immune cells in the microenvironment, there is limited anti-tumor immune response, even with newly developed immune checkpoint therapies. To overcome these challenges and enhance the efficacy of immunotherapies, a comprehensive understanding of the immune system in GBM and changes during disease progression is required. Here, we integrated multi-parameter flow cytometry and mass cytometry time of flight (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression. Utilizing multi-parameter flow cytometry analysis in a cohort of over 250 patients with brain tumors ranging from benign to malignant primary and metastatic, we found that GBM patients had a significant elevation in myeloid-derived suppressor cells (MDSCs) in blood, but not immunosuppressive T regulatory cells. We validated these findings in GBM patient tissue and found that increased numbers of MDSCs in recurrent GBM portended poor prognosis. CyTOF analysis of peripheral blood from a cohort of newly diagnosed GBM patients revealed that reduction in MDSC frequency over time is accompanied by a concomitant increase in dendritic cells and natural killer cells. This reduced MDSC profile was present in GBM patients with extended survival and was similar to that of low-grade glioma (LGG) patients. Our findings provide a rationale for developing strategies to target MDSCs, which are elevated in GBM patients and predict poor prognosis, either by directly targeting or by shifting the immune profile to induce differentiation toward the immune profile of LGGs.

scholarly journals Novel Therapeutic Strategies for Solid Tumor Based on Body’s Intrinsic Antitumor Immune System

2018 ◽  
Vol 47 (2) ◽  
pp. 441-457 ◽  
Author(s):  
Haifeng Duan
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Tumor Therapy ◽  
Suppressor Cells ◽  
Nutritional Supplement ◽  
Treg Cells ◽  
Tumor Burden ◽  
Antitumor Action

The accumulation of mutated somatic cells due to the incompetency of body’s immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body’s internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly.

scholarly journals Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors

2020 ◽  
Author(s):  
Sara Magri ◽  
Elena Masetto ◽  
Samantha Solito ◽  
Samuela Francescato ◽  
Elisa Belluzzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Functional Ability ◽  
Ex Vivo ◽  
Suppressor Cells ◽  
The Elderly ◽  
System Level ◽  
Low Grade ◽  
Age Related ◽  
Myeloid Progenitors

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.

scholarly journals Age-related sexual dimorphism on the longitudinal progression of blood immune cells in BALB/cByJ mice

2021 ◽  
Author(s):  
Cláudia Serre-Miranda ◽  
Susana Roque ◽  
Palmira Barreira-Silva ◽  
Claudia Nobrega ◽  
Neide Vieira ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Sexual Dimorphism ◽  
B Cells ◽  
Nk Cells ◽  
Mouse Models ◽  
Immune Cells ◽  
Age Related ◽  
The Impact ◽  
Over Time

Abstract The study of immune system aging is of relevance, considering its myriad of interactions and role in protecting and maintaining body homeostasis. While mouse models have been extensively used to study immune system aging, little is known on how the main immune populations progress over time and what is the impact of sex. To contribute to filling this gap, male and female BALB/cByJ mice were longitudinally evaluated, from 3 to 18 months old, for the main blood populations, assessed by flow cytometry. Using linear mixed-effect models, we observed that the percentages of neutrophils, monocytes, eosinophils and total natural killer (NK) cells increase with aging; while those of B cells, T cells (including CD4 + and CD8 + subsets) and Ly6C + NK cells, decrease. Males present higher percentages of neutrophils and classical monocytes Ly6C high over time, while females present higher percentages of total T cells, both CD4 + and CD8 +, eosinophils and NK cells. Males and females display similar percentages of B cells, even though with opposite accelerated progressions over time. This study revealed that mouse models recapitulate what is observed in humans during aging: an overall proportional decrease in the adaptive and an increase in the innate immune cells. Additionally, it uncovers an age-related sexual dimorphism in the proportion of immune cells in circulation, further strengthening the need to explore the impact of sex when addressing immune system aging using mouse models.

scholarly journals Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity

2020 ◽  
Author(s):  
Sara Falck-Jones ◽  
Sindhu Vangeti ◽  
Meng Yu ◽  
Ryan Falck-Jones ◽  
Alberto Cagigi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Severity ◽  
Respiratory Infections ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Inflammatory Conditions ◽  
Arginase 1 ◽  
T Cell Lymphopenia ◽  
Dependent Mechanism

The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFNγ production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.

scholarly journals Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1854 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  
Keyword(s):  
Immune System ◽  
Murine Model ◽  
Gut Microbiome ◽  
Inflammatory Marker ◽  
Low Grade ◽  
Host Immune System ◽  
Cancer Type ◽  
Microbiome Composition ◽  
Aged Mice ◽  
Age Related

Introduction.Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging.” While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model.Results.We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age.Discussion.Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.

scholarly journals Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives

2018 ◽  
Vol 19 (12) ◽  
pp. 3701 ◽  
Author(s):  
Rita Del Pinto ◽  
Claudio Ferri
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Common Denominator ◽  
Low Grade ◽  
Dna Targeting ◽  
Adaptive Immune ◽  
Immune System Dysfunction ◽  
Age Related ◽  
Genetic Modifications ◽  
Low Grade Inflammation

Low-grade chronic inflammation is a common denominator in atherogenesis and related diseases. Solid evidence supports the occurrence of an impairment in the innate and adaptive immune system with senescence, favoring the development of acute and chronic age-related diseases. Cardiovascular (CV) diseases (CVD), in particular, are a leading cause of death even at older ages. Inflammation-associated mechanisms that contribute to CVD development include dysregulated redox and metabolic pathways, genetic modifications, and infections/dysbiosis. In this review, we will recapitulate the determinants and consequences of the immune system dysfunction at older age, with particular focus on the CV system. We will examine the currently available and potential future strategies to counteract accelerated CV aging, i.e., nutraceuticals, probiotics, caloric restriction, physical activity, smoking and alcohol cessation, control of low-grade inflammation sources, senolytic and senescence-modulating drugs, and DNA-targeting drugs.

scholarly journals Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

2016 ◽  
Author(s):  
Melissa N. Conley ◽  
Carmen P. Wong ◽  
Kyle M. Duyck ◽  
Norman Hord ◽  
Emily Ho ◽  
...  
Keyword(s):  
Immune System ◽  
Murine Model ◽  
Gut Microbiome ◽  
Inflammatory Marker ◽  
Low Grade ◽  
Host Immune System ◽  
Cancer Type ◽  
Microbiome Composition ◽  
Aged Mice ◽  
Age Related

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.

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