scholarly journals An association between the gut microbiota and immune cell dynamics in humans

2019 ◽  
Author(s):  
Jonas Schluter ◽  
Jonathan U. Peled ◽  
Bradford P. Taylor ◽  
Melody Smith ◽  
Kate A. Markey ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Hematopoietic Cell Transplantation ◽  
Immune Cell ◽  
White Blood Cells ◽  
Anaerobic Bacteria ◽  
Human Immune System ◽  
Cell Dynamics ◽  
Cell Engraftment

ABSTRACTThe gut microbiota influences development and homeostasis of the mammalian immune system1–3, can alter immune cell compositions in mice4–7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8–12. Still, our understanding of how the microbiota modulates immune cells dynamics remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. We analyzed daily changes in white blood cells from 2,235 patients, and 10,680 longitudinal microbiota samples to identify bacteria associated with those changes. Bayesian inference and validation across patient cohorts revealed consistent associations between gut bacteria and white blood cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks. We contrasted the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism to estimate the potential of the microbiota to influence peripheral immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

scholarly journals Immunodepletion with Hypoxemia: A Potential High Risk Subtype of Coronavirus Disease 2019

2020 ◽  
Author(s):  
Lilei Yu ◽  
Yongqing Tong ◽  
Gaigai Shen ◽  
Aisi Fu ◽  
Yanqiu Lai ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
High Risk ◽  
Gut Microbiota ◽  
Dynamic Characteristics ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Disorder ◽  
Refractory Hypoxemia ◽  
Critical Patients

AbstractBackgroundThe outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia, and discuss the relationship between hypoxemia severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient.MethodsThis is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis.ResultsApart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia during the hospitalization, and the severity of hypoxemia was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died.ConclusionsWe discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis may be a high risk of fatal pneumonia.

XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE

2008 ◽  
Vol 31 (4) ◽  
pp. 3
Author(s):  
L Barrett ◽  
M Grant ◽  
R Liwski ◽  
K West
Keyword(s):  
Immune System ◽  
Peripheral Blood ◽  
Lymphoid Tissue ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
White Blood Cells ◽  
Interleukin 10 ◽  
Healthy Individuals ◽  
Human Immune System ◽  
Healthy Humans

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro. Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well. Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL. Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.

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 Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

2021 ◽  
Vol 14 ◽  
Author(s):  
Elise Liu ◽  
Léa Karpf ◽  
Delphine Bohl
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune System ◽  
Frontotemporal Dementia ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Cell Types ◽  
Induced Pluripotent ◽  
Different Cell Types ◽  
Lateral Sclerosis

Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

scholarly journals Human immune system variation during one year

2020 ◽  
Author(s):  
Tadepally Lakshmikanth ◽  
Sayyed Auwn Muhammad ◽  
Axel Olin ◽  
Yang Chen ◽  
Jaromir Mikes ◽  
...  
Keyword(s):  
Immune System ◽  
Individual Variation ◽  
Immune Cell ◽  
Metabolic Health ◽  
Individual Feature ◽  
Human Immune System ◽  
Principal Curve ◽  
Human Immune ◽  
One Year ◽  
Over Time

SUMMARYThe human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components, and the inference of global regulatory principles. Here we present a longitudinal, systems-level analysis in 99 healthy adults, 50 to 65 years of age and sampled every 3rd month during one year. We describe the structure of inter-individual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited markers of poor metabolic health suggestive of a functional link between metabolic and immunologic homeostatic regulation.HIGHLIGHTSLongitudinal variation in immune cell composition during one yearInter-individual variation can be described along a principal curveImmune cell and protein relationships are inferredVariability over time is an individual feature correlating with markers of poor metabolic health

scholarly journals Search for receptors in immune cells that bind cancer cell antigens and their activation in silent cases

2019 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Immune System ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immune Receptor

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.

scholarly journals Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claire Healy ◽  
Natalia Munoz-Wolf ◽  
Janné Strydom ◽  
Lynne Faherty ◽  
Niamh C. Williams ◽  
...  
Keyword(s):  
Immune System ◽  
Trace Metals ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Immune Cells ◽  
Immune Cell ◽  
Redox Activity ◽  
Nutritional Immunity ◽  
Airway Microbiome ◽  
The Impact

AbstractNutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.

scholarly journals Recent Advancements and Applications of Human Immune System Mice in Preclinical Immuno-Oncology

2019 ◽  
Vol 48 (2) ◽  
pp. 302-316 ◽  
Author(s):  
Michelle Curran ◽  
Maelle Mairesse ◽  
Alba Matas-Céspedes ◽  
Bethany Bareham ◽  
Giovanni Pellegrini ◽  
...  
Keyword(s):  
Immune System ◽  
New Technologies ◽  
Immune Cell ◽  
Human Immune System ◽  
Immunodeficient Mice ◽  
Graft Versus Host ◽  
Human Immune ◽  
And Function ◽  
Human Cytokines

Significant advances in immunotherapies have resulted in the increasing need of predictive preclinical models to improve immunotherapeutic drug development, treatment combination, and to prevent or minimize toxicity in clinical trials. Immunodeficient mice reconstituted with human immune system (HIS), termed humanized mice or HIS mice, permit detailed analysis of human immune biology, development, and function. Although this model constitutes a great translational model, some aspects need to be improved as the incomplete engraftment of immune cells, graft versus host disease and the lack of human cytokines and growth factors. In this review, we discuss current HIS platforms, their pathology, and recent advances in their development to improve the quality of human immune cell reconstitution. We also highlight new technologies that can be used to better understand these models and how improved characterization is needed for their application in immuno-oncology safety, efficacy, and new modalities therapy development.

scholarly journals Effects of low dose radiation on immune cells subsets and cytokines in mice

2020 ◽  
Vol 9 (3) ◽  
pp. 249-262
Author(s):  
Xiaochang Liu ◽  
Zheng Liu ◽  
Duo Wang ◽  
Yang Han ◽  
Sai Hu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Low Dose ◽  
White Blood Cells ◽  
Whole Body ◽  
Low Dose Radiation ◽  
Dose Irradiation ◽  
Significant Difference ◽  
Dose Radiation

Abstract Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.

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