scholarly journals Gut Microbiome and Organ Fibrosis

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 352
Author(s):  
Carolina F. F. A. Costa ◽  
Benedita Sampaio-Maia ◽  
Ricardo Araujo ◽  
Diana S. Nascimento ◽  
Joana Ferreira-Gomes ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Organ Damage ◽  
Pathological Process ◽  
The Body ◽  
Intestinal Fibrosis ◽  
Immune Mediated ◽  
Major Player ◽  
Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

scholarly journals The gut microbiome in sickle cell disease: Characterization and potential implications

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255956
Author(s):  
Hassan Brim ◽  
James Taylor ◽  
Muneer Abbas ◽  
Kimberly Vilmenay ◽  
Mohammad Daremipouran ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Gut Microbiome ◽  
Tissue Injury ◽  
Organ Damage ◽  
Composition Analysis ◽  
Cell Disease ◽  
Blood Disorder ◽  
Major Player ◽  
Next Generation Sequencing Ngs

Background Sickle Cell Disease (SCD) is an inherited blood disorder that leads to hemolytic anemia, pain, organ damage and early mortality. It is characterized by polymerized deoxygenated hemoglobin, rigid sickle red blood cells and vaso-occlusive crises (VOC). Recurrent hypoxia-reperfusion injury in the gut of SCD patients could increase tissue injury, permeability, and bacterial translocation. In this context, the gut microbiome, a major player in health and disease, might have significant impact. This study sought to characterize the gut microbiome in SCD. Methods Stool and saliva samples were collected from healthy controls (n = 14) and SCD subjects (n = 14). Stool samples were also collected from humanized SCD murine models including Berk, Townes and corresponding control mice. Amplified 16S rDNA was used for bacterial composition analysis using Next Generation Sequencing (NGS). Pairwise group analyses established differential bacterial groups at many taxonomy levels. Bacterial group abundance and differentials were established using DeSeq software. Results A major dysbiosis was observed in SCD patients. The Firmicutes/Bacteroidetes ratio was lower in these patients. The following bacterial families were more abundant in SCD patients: Acetobacteraceae, Acidaminococcaceae, Candidatus Saccharibacteria, Peptostreptococcaceae, Bifidobacteriaceae, Veillonellaceae, Actinomycetaceae, Clostridiales, Bacteroidacbactereae and Fusobacteriaceae. This dysbiosis translated into 420 different operational taxonomic units (OTUs). Townes SCD mice also displayed gut microbiome dysbiosis as seen in human SCD. Conclusion A major dysbiosis was observed in SCD patients for bacteria that are known strong pro-inflammatory triggers. The Townes mouse showed dysbiosis as well and might serve as a good model to study gut microbiome modulation and its impact on SCD pathophysiology.

scholarly journals Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases

2019 ◽  
Vol 20 (14) ◽  
pp. 3394 ◽  
Author(s):  
Kübra Bunte ◽  
Thomas Beikler
Keyword(s):  
Innate Immunity ◽  
Th17 Cells ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Immune Mediated ◽  
Bowel Diseases

Innate immunity represents the semi-specific first line of defense and provides the initial host response to tissue injury, trauma, and pathogens. Innate immunity activates the adaptive immunity, and both act highly regulated together to establish and maintain tissue homeostasis. Any dysregulation of this interaction can result in chronic inflammation and autoimmunity and is thought to be a major underlying cause in the initiation and progression of highly prevalent immune-mediated inflammatory diseases (IMIDs) such as psoriasis, rheumatoid arthritis, inflammatory bowel diseases among others, and periodontitis. Th1 and Th2 cells of the adaptive immune system are the major players in the pathogenesis of IMIDs. In addition, Th17 cells, their key cytokine IL-17, and IL-23 seem to play pivotal roles. This review aims to provide an overview of the current knowledge about the differentiation of Th17 cells and the role of the IL-17/IL-23 axis in the pathogenesis of IMIDs. Moreover, it aims to review the association of these IMIDs with periodontitis and briefly discusses the therapeutic potential of agents that modulate the IL-17/IL-23 axis.

scholarly journals Physical phenotype of blood cells is altered in COVID-19

2021 ◽  
Author(s):  
Markéta Kubánková ◽  
Bettina Hohberger ◽  
Jakob Hoffmanns ◽  
Julia Fürst ◽  
Martin Herrmann ◽  
...  
Keyword(s):  
Blood Cells ◽  
Inflammatory Diseases ◽  
Vascular Occlusion ◽  
Cell Types ◽  
Organ Damage ◽  
Clinical Syndrome ◽  
The Body ◽  
Physical Parameters ◽  
Physical Changes

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than 4 million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in erythrocyte deformability, lymphocyte stiffness, monocyte size, and neutrophil size and deformability. While some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

scholarly journals THE STATE OF THE CELLS OF THE IMMUNE SYSTEM IN EXPERIMENTAL IMMUNE-MEDIATED INFLAMMATION OF VARIOUS GENESIS

2021 ◽  
Vol 17 (2) ◽  
pp. 20-26
Author(s):  
S.I. Pavlovych ◽  
N.G. Grushka ◽  
O.A. Kondratska ◽  
N.O. Krasutska ◽  
R.I. Yanchii
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Membrane Integrity ◽  
Genotoxic Stress ◽  
Pathological Process ◽  
The Body ◽  
Cellular Mechanisms ◽  
Nonspecific Resistance ◽  
Immune Mediated ◽  
Endotoxemia Model

Relevance. Immune-mediated inflammation of various genesis plays a significant pathogenetic role in autoimmune, allergic, inflammatory and infectious diseases. The objective of the work was a comparative study of the functional status and pathways of cell death of natural and adaptive immunity in mice under the conditions of experimental hyperimmunocomplexemia and endotoxemia to identify the features and common cellular mechanisms of these pathologies. Materials and methods. Hyperimmunocomplexemia was simulated by six-fold immunization of female mice with increasing doses of the antigen, bovine serum albumin (BSA), once a week; the endotoxemia model was induced by the administration of lipopolysaccharide (LPS). Results. The use of both BSA and LPS led to a systemic inflammatory process with significant neutrophilia with a shift of the leukogram to the left. There was a significant increase in the functional and metabolic activity of nonspecific resistance cells. Genotoxic stress was observed in thymus cells and lymph nodes with significant DNA damage, decreased viability, and a significant increase in necrotic death. Violation of the plasma membrane integrity of primary alteration and the release of the cellular content outside has a strong pro-inflammatory and immunogenic effect, which can lead to further intensification of the disease and an increase in its duration with a tendency to chronicity of the pathological process. Conclusions. Thus, both models are characterized by the development of immune-inflammatory processes that lead to significant DNA damage and cell death, which can cause a new round of intensification of necrotic, inflammatory and autoimmune reactions in the body.

scholarly journals C3 AND C4 COMPLEMENT – BIOMARKERS FOR PROGNOSIS OF TREATMENT OF TNF-BLOKERS

2019 ◽  
Vol 32 (2) ◽  
pp. 247-250
Author(s):  
Stanislava Popova ◽  
Mariela Geneva
Keyword(s):  
Immune System ◽  
Complement System ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Response Prediction ◽  
The Body ◽  
Control Group ◽  
Phagocytic Cells ◽  
Immune System Activation ◽  
The Complement System

Introduction: The complement system adds antibodies and helps phagocytic cells to destroy pathogens from the body. This is part of a congenital immune system that is not adaptive and does not change over the individual life. However, complement can be "triggered" by the adaptive immune system. The complement system is the main effector of the humoral patr of the immune system. Activation of complement results in opsonization, chemotaxis and cytolysis. Regulation of the complement system can control inflammatory diseases including psoriatic arthritis and vice versa, complement fixation disorders can lead to illness. Treatment with anti-TNF blokers complement activity in patients with inflammatory joint diseases.Objective: To investigate C3, C4 fractions of complement, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement the response prediction and monitoring of anti-TNF treatment in patients with psoriatic arthritis.Materials and Methods: 36 patients were included sequentially before treatment with TNF-a-blokers. C3, C4, ESR, CRP were assessed at baseline at 6 and 12 months after initiation of treatment with TNF-α blockers. The activity of the disease is measured by the DARSA disease activity scale, the responses being compared with a control group of persons similar in gender and age. Statistical data processing was performed using the SPSS v25.Results and conclusions: According to the results obtained, C3 and C4 were significantly higher than controls at initiation of treatment (C3 111.3 ± 30.8, C4 91.9 ± 12.4 mg / dl, controls 19.1 ± 8.3 mg / dl, 10.2 ± 5.6 mg / dl p = 0.001, p = 0.001). At 6 and 12 months of follow-up, 76.2% of patients had a reduction in the level of C3 and C4 (p = 0.002, 0.001, respectively). It was found that higher baseline levels of C3 were associated with higher DARSA values at 6 and 12 months.Conclusion: The study of the C3 and C4 complement fractions can be used as biomarkers to estimate the prognosis of TNF-blocker therapy.

scholarly journals Interleukin-22 Influences the Th1/Th17 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannes Lindahl ◽  
Tomas Olsson
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Cell Polarization ◽  
The Body ◽  
Innate Immune ◽  
Interleukin 22 ◽  
Downstream Effects ◽  
Wide Range

Interleukin-22 (IL-22) is secreted by a wide range of immune cells and its downstream effects are mediated by the IL-22 receptor, which is present on non-immune cells in many organs throughout the body. IL-22 is an inflammatory mediator that conditions the tissue compartment by upregulating innate immune responses and is also a homeostatic factor that promotes tissue integrity and regeneration. Interestingly, the IL-22 system has also been linked to many T cell driven inflammatory diseases. Despite this, the downstream effects of IL-22 on the adaptive immune system has received little attention. We have reviewed the literature for experimental data that suggest IL-22 mediated effects on T cells, either transduced directly or via mediators expressed by innate immune cells or non-immune cells in response to IL-22. Collectively, the reviewed data indicate that IL-22 has a hitherto unappreciated influence on T helper cell polarization, or the secretion of signature cytokines, that is context dependent but in many cases results in a reduction of the Th1 type response and to some extent promotion of regulatory T cells. Further studies are needed that specifically address these aspects of IL-22 signaling, which can benefit the understanding and treatment of a wide range of diseases.

scholarly journals Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

2016 ◽  
Vol 113 (7) ◽  
pp. 1865-1870 ◽  
Author(s):  
Sonika Patial ◽  
Alan D. Curtis ◽  
Wi S. Lai ◽  
Deborah J. Stumpo ◽  
Georgette D. Hill ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Genetic Locus ◽  
The Body ◽  
Cultured Fibroblasts ◽  
Proinflammatory Mediators ◽  
Immune Mediated ◽  
Mouse Tissues ◽  
Attractive Therapeutic Target ◽  
Specific Mrnas ◽  
Mrna Binding

Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate–rich elements (AREs) in the 3′-untranslated regions (3′UTRs) of specific mRNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTPΔARE) in which a 136-base instability motif in the 3′UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS-stimulated macrophages and increased levels of TTP protein in mouse tissues. TTPΔARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases.

scholarly journals A “strange” case of COPD

2015 ◽  
Vol 4 (3S) ◽  
pp. 63-66
Author(s):  
Laura Massarelli ◽  
Valerio Tomaselli ◽  
Carlo Bussolino ◽  
Valter Saracco
Keyword(s):  
Celiac Disease ◽  
Respiratory Tract ◽  
Bacterial Infections ◽  
B Lymphocyte ◽  
Inflammatory Diseases ◽  
Organ Damage ◽  
Positive Influence ◽  
Lymphoid Organ ◽  
The Body ◽  
Recurrent Infections

Common variable immunodeficiency (CVID) is a rare syndrome, characterized by hypogammaglobulinemia and limited antibody responses due to either impaired B-lymphocyte development or B-cell responses to T-lymphocyte signals. CVID is frequently associated with bacterial infections, particularly against respiratory tract, that could determine a permanent organ damage (COPD, asthma), increased incidence of both autoimmune diseases and cancer, high prevalence of gastrointestinal inflammatory diseases (ulcerative colitis, Crohn’s disease, celiac disease), lymphoproliferative and granulomatous diseases. Given that the gastrointestinal tract is the largest lymphoid organ in the body, it’s not surprising that intestinal diseases are common in immunodeficiency. CVID is considered a congenital condition but it is usually diagnosed in adulthood. We describe the case of a 43-year-old man affected by recurrent infections of respiratory tract with CVID, celiac disease and type 1 diabetes. With the exclusion of gluten from the diet, patient achieved an improvement of serum level of immunoglobulins and a reduction of recurrent infections. This fact suggests that the interruption of the gluten stimulus could have a positive influence on the other diseases, improving the metabolic compensation and stabilizing the immune system.

scholarly journals Ways to prevent acute viral infection and its bacterial complications

2021 ◽  
pp. 103-109
Author(s):  
G. V. Lavrenova ◽  
M. S. Zaynchukovskiy ◽  
K. T. Zhamakochyan ◽  
M. I. Malysheva
Keyword(s):  
Respiratory Tract ◽  
Viral Infection ◽  
Viral Infections ◽  
Chronic Sinusitis ◽  
Inflammatory Diseases ◽  
Pathological Process ◽  
The Body ◽  
Stress Factors ◽  
Upper Respiratory Tract ◽  
Starting Point

Viruses of the ARVI group that are tropic to the epithelium of the upper respiratory tract are able to inhibit the function of the mucociliary system to a certain extent, which contributes to the attachment of bacterial infection. Thus, in respiratory inflammatory diseases, the infection is often combined. This means, that the question about approaches to treatment at the stage of prevention of the development of complications of ARVI arises. A significant increase in the relapse of chronic sinusitis has been observed over the past 10 years. According to A.I. Kryukov et al. the relapse of inflammatory diseases of the paranasal sinuses, the chronic process has no tendency to decrease, aided by the unfavorable ecological situation, the growth of allergic and viral respiratory diseases, poor nutrition to which the body is not evolutionarily adapted. Worsening of chronic sinusitis contributes to many factors, but the starting point is almost always viral infections. Relapse, as a rule, begins with viral rhinitis, which is rarely an independent disease. Most often, a runny nose is a symptom of ARVI or ARI (influenza, parainfluenza, adenovirus infection, etc.). The entrance gate of infection is the epithelial cells of the respiratory tract. The main pathological process in sensitive cells develops both as a result of the penetration of the virus from the outside, and due to the activation of latent or chronic viral infection under the influence of various factors, including other infection.The appointment of drugs with anti-inflammatory, immunomodulatory, adaptogenic activity is one of the promising options for the prevention of both primary viral infection and the development of bacterial complications.We have included a drug that combines adaptogenic and immunomodulatory activities in the treatment of chronic sinusitis. Trekrezan belongs to the group of adaptogens – low-toxic compounds, it is recommended as a measure for the treatment and prevention of viral infections and increasing resistance to various stress factors (hypoxia, hypothermia) and adverse environmental effects. 

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