scholarly journals Gut microbiota and systemic immunity in health and disease

2020 ◽  
Author(s):  
Bernard C Lo ◽  
Grace Y Chen ◽  
Gabriel Núñez ◽  
Roberta Caruso
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cell ◽  
Cell Responses ◽  
Complex Interactions ◽  
Intestinal Physiology ◽  
Health And Disease ◽  
Gut Symbionts ◽  
Underlying Mechanisms ◽  
Mammalian Intestine

Abstract The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. Although the influence of the gut microbiota on intestinal physiology and immunity is well known, mounting evidence suggests a key role for intestinal symbionts in controlling immune cell responses and development outside the gut. Although the underlying mechanisms by which the gut symbionts influence systemic immune responses remain poorly understood, there is evidence for both direct and indirect effects. In addition, the gut microbiota can contribute to immune responses associated with diseases outside the intestine. Understanding the complex interactions between the gut microbiota and the host is thus of fundamental importance to understand both immunity and human health.

scholarly journals Gut Microbiota and Host Metabolism: From Proof of Concept to Therapeutic Intervention

2021 ◽  
Vol 9 (6) ◽  
pp. 1302
Author(s):  
Patrice D. Cani ◽  
Emilie Moens de Hase ◽  
Matthias Van Hul
Keyword(s):  
Gut Microbiota ◽  
Research Field ◽  
Proof Of Concept ◽  
Clinical Implementation ◽  
Science Area ◽  
Microbiome Research ◽  
Fast Pace ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Host Metabolism

The field of the gut microbiota is still a relatively young science area, yet many studies have already highlighted the translational potential of microbiome research in the context of human health and disease. However, like in many new fields, discoveries are occurring at a fast pace and have provided new hope for the development of novel clinical applications in many different medical conditions, not in the least in metabolic disorders. This rapid progress has left the field vulnerable to premature claims, misconceptions and criticism, both from within and outside the sector. Tackling these issues requires a broad collaborative effort within the research field and is only possible by acknowledging the difficulties and challenges that are faced and that are currently hindering clinical implementation. These issues include: the primarily descriptive nature of evidence, methodological concerns, disagreements in analysis techniques, lack of causality, and a rather limited molecular-based understanding of underlying mechanisms. In this review, we discuss various studies and models that helped identifying the microbiota as an attractive tool or target for developing various translational applications. We also discuss some of the limitations and try to clarify some common misconceptions that are still prevalent in the field.

scholarly journals Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

Gut ◽  
2017 ◽  
Vol 67 (5) ◽  
pp. 847-859 ◽  
Author(s):  
Allison Cabinian ◽  
Daniel Sinsimer ◽  
May Tang ◽  
Youngsoon Jang ◽  
Bongkum Choi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Premature Death ◽  
Enteric Pathogens ◽  
Immune Protection ◽  
Intestinal Immunity ◽  
Cell Responses ◽  
And Function

BackgroundInteractions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.AimWe have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.MethodsExpression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium.ResultsSLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.ConclusionsSLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

scholarly journals TCR Transgenic Mice: A Valuable Tool for Studying Viral Immunopathogenesis Mechanisms

2020 ◽  
Vol 21 (24) ◽  
pp. 9690
Author(s):  
Yong-Bin Cho ◽  
In-Gu Lee ◽  
Yong-Hyun Joo ◽  
So-Hee Hong ◽  
Young-Jin Seo
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Global Economy ◽  
Viral Infections ◽  
Cell Receptor ◽  
Cell Responses ◽  
Significant Burden ◽  
Underlying Mechanisms ◽  
Remarkable Progress

Viral infectious diseases are a significant burden on public health and the global economy, and new viral threats emerge continuously. Since CD4+ and CD8+ T cell responses are essential to eliminating viruses, it is important to understand the underlying mechanisms of anti-viral T cell-mediated immunopathogenesis during viral infections. Remarkable progress in transgenic (Tg) techniques has enabled scientists to more readily understand the mechanisms of viral pathogenesis. T cell receptor (TCR) Tg mice are extremely useful in studying T cell-mediated immune responses because the majority of T cells in these mice express specific TCRs for partner antigens. In this review, we discuss the important studies utilizing TCR Tg mice to unveil underlying mechanisms of T cell-mediated immunopathogenesis during viral infections.

scholarly journals Microbiota and metabolism: what's new in 2018?

2018 ◽  
Vol 315 (1) ◽  
pp. E1-E6 ◽  
Author(s):  
Alexis Bretin ◽  
Andrew T. Gewirtz ◽  
Benoit Chassaing
Keyword(s):  
Gut Microbiota ◽  
Metabolic Health ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Made In

The concept that the gut microbiota plays a broadly important role in health and disease in general, and metabolic health in particular, is now well established. However, many of the underlying mechanisms remain poorly understood while approaches to reliably manipulate the microbiota to promote health have not yet been clearly defined. Nonetheless, progress in these areas is steadily accelerating. Herein, we review select areas of progress that have been made in the last year that should hasten the era in which the microbiota can be therapeutically manipulated to promote metabolic health.

scholarly journals Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Daniel Crean ◽  
Evelyn P. Murphy
Keyword(s):  
Nuclear Receptors ◽  
Cell Cycle Progression ◽  
Stromal Cell ◽  
Immune Cell ◽  
Cycle Progression ◽  
Cell Responses ◽  
Inflammatory Conditions ◽  
Health And Disease

The NR4A1–NR4A3 (Nur77, Nurr1, and Nor-1) subfamily of nuclear receptors is a group of immediate early genes induced by a pleiotropy of stimuli including peptide hormones, growth factors, cytokines, inflammatory, and physiological stimuli, and cellular stress. NR4A receptors function as potent sensors of changes in the cellular microenvironment to control physiological and pathological processes through genomic and non-genomic actions. NR4A receptors control metabolism and cardiovascular and neurological functions and mediate immune cell homeostasis in inflammation and cancer. This receptor subfamily is increasingly recognized as an important molecular connection between chronic inflammation, altered immune cell responses, and cancer development. In this review, we examine how transcriptome analysis identified NR4A1/NR4A2 receptors as transcriptional regulators in mesenchymal stromal cell (MSC) migration, cell cycle progression, and cytokine production to control local immune responses. In chronic inflammatory conditions, such as rheumatoid arthritis, NR4A receptors have been shown to modify the activity of MSC and fibroblast-like stromal cells to regulate synovial tissue hyperplasia, pathological angiogenesis, and cartilage turnover in vivo. Additionally, as NR4A1 has been observed as a major transcriptional regulator in tumor–stromal communication controlling tumorigenesis, we discuss how advances in the pharmacological control of these receptors lead to important new mechanistic insights into understanding the role of the tumor microenvironment in health and disease.

scholarly journals Microbiota and Colorectal Cancer: From Gut to Bedside

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Silva ◽  
Valentina Brunner ◽  
Markus Tschurtschenthaler
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Tumour Progression ◽  
Cellular Transformation ◽  
Intestinal Epithelial ◽  
Therapeutic Drugs ◽  
New Findings ◽  
Current Therapies ◽  
Health And Disease

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host’s gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

scholarly journals Mapping and Characterization of HCMV-Specific Unconventional HLA-E-Restricted CD8 T Cell Populations and Associated NK and T Cell Responses Using HLA/Peptide Tetramers and Spectral Flow Cytometry

2021 ◽  
Vol 23 (1) ◽  
pp. 263
Author(s):  
Amélie Rousselière ◽  
Laurence Delbos ◽  
Céline Bressollette ◽  
Maïlys Berthaume ◽  
Béatrice Charreau
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Hcmv Infection ◽  
Immune Cell ◽  
Nk Cell ◽  
Spectral Flow ◽  
Cell Responses

HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative analysis of their phenotype. To map the various anti-HCMV cellular responses, we used a combination of three HLApeptide tetramer complexes (HLA-EVMAPRTLIL, HLA-EVMAPRSLLL, and HLA-A2NLVPMVATV) and antibodies for 18 surface markers (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CD57, CD158, NKG2A, NKG2C, CCR7, TCRγδ, TCRγδ2, CX3CR1, KLRG1, 2B4, and PD-1) in a 20-color spectral flow cytometry analysis. This immunostaining protocol was applied to PBMCs isolated from HCMV- and HCMV+ individuals. Our workflow allows the efficient determination of events featuring HCMV infection such as CD4/CD8 ratio, CD8 inflation and differentiation, HCMV peptide-specific HLA-EUL40 and HLA-A2pp65CD8 T cells, and expansion of γδT and NK subsets including δ2-γT and memory-like NKG2C+CD57+ NK cells. Each subset can be further characterized by the expression of 2B4, PD-1, KLRG1, CD45RA, CCR7, CD158, and NKG2A to achieve a fine-tuned mapping of HCMV immune responses. This assay should be useful for the analysis and monitoring of T-and NK cell responses to HCMV infection or vaccines.

scholarly journals Contribution of Gut Bacteria to Liver Pathobiology

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Gakuhei Son ◽  
Michael Kremer ◽  
Ian N. Hines
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Tissue Injury ◽  
Gut Bacteria ◽  
First Line ◽  
Ischemic Tissue ◽  
Toxin Exposure ◽  
Broad Array ◽  
Health And Disease ◽  
The Relationship

Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells) to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc.), these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.

scholarly journals Dietary L-Tryptophan Regulates Colonic Serotonin Homeostasis in Mice with Dextran Sodium Sulfate-Induced Colitis

2020 ◽  
Vol 150 (7) ◽  
pp. 1966-1976 ◽  
Author(s):  
Bin Wang ◽  
Shiqiang Sun ◽  
Moyan Liu ◽  
Hui Chen ◽  
Ning Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drinking Water ◽  
Immune Responses ◽  
Sodium Sulfate ◽  
Serotonin Receptor ◽  
Immune Cell ◽  
Dextran Sodium Sulfate ◽  
Stat3 Signaling ◽  
Underlying Mechanisms ◽  
Cell Phenotypes

ABSTRACT Background L-tryptophan (Trp) has been reported to regulate gut immune responses during inflammation. However, the underlying mechanisms are largely unknown. Objective We investigated the role of Trp supplementation on the serotonin receptor (HTR)-mediated immune response in the colon of mice with dextran sodium sulfate (DSS)-induced colitis. Methods In Experiment 1, male C57BL/6 mice were randomly assigned to 1 of 4 groups: Control (Con) or L-Trp supplementation [0.1 mg/(g body weight·d) in drinking water] (Trp) with (+DSS) or without 2% DSS in drinking water from days 8 to 14 of the 17-d study. In Experiments 2 and 3, Trp + DSS (Expt. 2) or DSS (Expt. 3) mice were treated as described above and subcutaneously administered with HTR1A or HTR4 antagonists (or their combination) or an HTR2 agonist from days 8 to 14 of the 15-d study. Changes in immune cell phenotypes, inflammatory mediators, and related cell signaling molecules were assessed by flow cytometry, real-time PCR, or Western blot. The mRNA abundances of Trp hydroxylase (Tph1), serotonin reuptake transporter (Slc6a4), and Htr in the colon were also assessed. Results Trp supplementation before DSS treatment upregulated the expression of colonic Slc6a4 (0.49 compared with 0.30), Htr1a (1.14 compared with 0.65), and Htr4 (1.08 compared with 0.70), downregulated the expression of Htr2a (1.54 compared with 1.89), and decreased the colonic serotonin concentration (11.5 compared with 14.8 nmol/g tissue) (P < 0.01). Trp regulated the DSS-induced immune response partly through attenuating the activation of toll-like receptor 4 (TLR4)-STAT3 signaling and nucleus p-65. Either an HTR2 agonist or HTR1A and HTR4 antagonists reversed the effects of Trp. Conclusions In mice treated with DSS, Trp supplementation before DSS administration improved colonic immune responses partly by reducing colonic serotonin and subsequent interactions with HTR1A and HTR4, which are known to be present on neutrophils and macrophages.

Sign in / Sign up

Export Citation Format

Share Document