Developmental thyroid disruption causes long-term impacts on immune cell function and transcriptional responses to pathogen in a small fish model

AbstractCurrent evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from < 1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood (5–7 months post hatch) at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases (1.2-fold) in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load or pathogen resistance were noted. Overall, these results suggest that early life stage TH suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development, which can occur in response to chemicals present in the environment, may have lasting effects on immune function in adulthood.

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Early Life Stage Thyroid Hormone Disruption Causes Long-Term Impacts On Immune Cell Function And Transcriptional Responses To Pathogen In The Fathead Minnow (Pimephales Promelas)

10.21203/rs.3.rs-519910/v1 ◽

2021 ◽

Author(s):

Leah M. Thornton Hampton ◽

Miranda G. Finch ◽

Christopher J. Martyniuk ◽

Barney J. Venables ◽

Marlo K. Sellin Jeffries

Keyword(s):

Immune System ◽

Thyroid Hormone ◽

Immune Function ◽

Early Life ◽

Cell Function ◽

Immune Cell ◽

Life Stage ◽

Bacterial Load ◽

Early Life Stage

Abstract Current evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from <1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load nor pathogen resistance were noted. Overall, these results suggest that early life stage thyroid hormone suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development may have lasting effects on immune function in adulthood.

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Cellular and metabolic mechanisms of nutrient actions in immune function

Nutrition and Diabetes ◽

10.1038/s41387-021-00162-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip Newsholme

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Vitamin D ◽

Immune System ◽

Cell Function ◽

Immune Cell ◽

Cell Structure ◽

Nutritional Intervention ◽

Immune Cell Function ◽

And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

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Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

Frontiers in Medicine ◽

10.3389/fmed.2021.745789 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mohammed M. Almutairi ◽

Farzane Sivandzade ◽

Thamer H. Albekairi ◽

Faleh Alqahtani ◽

Luca Cucullo

Keyword(s):

Immune System ◽

Molecular Mechanisms ◽

Potential Role ◽

Immune Cell ◽

Clinical Manifestations ◽

Cell Infiltration ◽

Cellular Mechanisms ◽

Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

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The Immune System Can Hear Noise

Frontiers in Immunology ◽

10.3389/fimmu.2020.619189 ◽

2021 ◽

Vol 11 ◽

Author(s):

Andi Zhang ◽

Tianyuan Zou ◽

Dongye Guo ◽

Quan Wang ◽

Yilin Shen ◽

...

Keyword(s):

Immune System ◽

Adverse Effects ◽

Immune Function ◽

Noise Exposure ◽

The Body ◽

Intensity Noise ◽

Short Term ◽

Non Hodgkin Lymphoma ◽

Exposure During Pregnancy

As a stressor widely existing in daily life, noise can cause great alterations to the immune system and result in many physical and mental disorders, including noise-induced deafness, sleep disorders, cardiovascular diseases, endocrine diseases and other problems. The immune system plays a major role in maintaining homeostasis by recognizing and removing harmful substances in the body. Many studies have shown that noise may play vital roles in the occurrence and development of some immune diseases. In humans, both innate immunity and specific immunity can be influenced by noise, and different exposure durations and intensities of noise may exert various effects on the immune system. Short-term or low-intensity noise can enhance immune function, while long-term or high-intensity noise suppresses it. Noise can lead to the occurrence of noise-induced hearing loss (NIHL) through the production of autoantibodies such as anti-Hsp70 and anti-Hsp60 and exert adverse effects related to other immune-related diseases such as some autoimmune diseases and non-Hodgkin lymphoma. The neuroendocrine system, mainly including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system, is involved in the mechanisms of immune-related diseases induced by noise and gut microbiota dysfunction. In addition, noise exposure during pregnancy may be harmful to the immune system of the fetus. On the other hand, some studies have shown that music can improve immune function and alleviate the adverse effects caused by noise.

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Reduction of leucocyte cell surface disulfide bonds during immune activation is dynamic as revealed by a quantitative proteomics workflow (SH-IQ)

Open Biology ◽

10.1098/rsob.180079 ◽

2018 ◽

Vol 8 (9) ◽

pp. 180079

Author(s):

Monika Stegmann ◽

A. Neil Barclay ◽

Clive Metcalfe

Keyword(s):

Immune System ◽

Cell Surface ◽

Immune Activation ◽

Disulfide Bonds ◽

Cell Function ◽

Immune Cell ◽

Surface Proteins ◽

Cell Surface Receptors ◽

Surface Receptors ◽

Pathogen Clearance

Communication through cell surface receptors is crucial for maintaining immune homeostasis, coordinating the immune response and pathogen clearance. This is dependent on the interaction of cell surface receptors with their ligands and requires functionally active conformational states. Thus, immune cell function can be controlled by modulating the structure of either the receptor or the ligand. Reductive cleavage of labile disulfide bonds can mediate such an allosteric change, resulting in modulation of the immune system by a hitherto little studied mechanism. Identifying proteins with labile disulfide bonds and determining the extent of reduction is crucial in elucidating the functional result of reduction. We describe a mass spectrometry-based method—thiol identification and quantitation (SH-IQ)—to identify, quantify and monitor such reduction of labile disulfide bonds in primary cells during immune activation. These results provide the first insight into the extent and dynamics of labile disulfide bond reduction in leucocyte cell surface proteins upon immune activation. We show that this process is thiol oxidoreductase-dependent and mainly affects activatory (e.g. CD132, SLAMF1) and adhesion (CD44, ICAM1) molecules, suggesting a mechanism to prevent over-activation of the immune system and excessive accumulation of leucocytes at sites of inflammation.

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Transcriptomic Responses of Bisphenol S Predict Involvement of Immune Function in the Cardiotoxicity of Early Life-Stage Zebrafish (Danio rerio)

Environmental Science & Technology ◽

10.1021/acs.est.9b06213 ◽

2019 ◽

Vol 54 (5) ◽

pp. 2869-2877 ◽

Cited By ~ 5

Author(s):

Wenhui Qiu ◽

Bei Chen ◽

Justin B. Greer ◽

Jason T. Magnuson ◽

Ying Xiong ◽

...

Keyword(s):

Immune Function ◽

Danio Rerio ◽

Early Life ◽

Life Stage ◽

Early Life Stage ◽

Bisphenol S ◽

Transcriptomic Responses

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Long-Term Effects of Experimental Human Endotoxemia on Immune Cell Function

Shock ◽

10.1097/shk.0000000000001222 ◽

2019 ◽

Vol 51 (6) ◽

pp. 678-689 ◽

Cited By ~ 2

Author(s):

Yessica Alina Rodriguez-Rosales ◽

Matthijs Kox ◽

Esther van Rijssen ◽

Bram van Cranenbroek ◽

Marina van Welie ◽

...

Keyword(s):

Cell Function ◽

Immune Cell ◽

Immune Cell Function ◽

Long Term Effects ◽

Human Endotoxemia

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EZH2 function in immune cell development

Biological Chemistry ◽

10.1515/hsz-2019-0436 ◽

2020 ◽

Vol 401 (8) ◽

pp. 933-943 ◽

Cited By ~ 5

Author(s):

Stephen L. Nutt ◽

Christine Keenan ◽

Michaël Chopin ◽

Rhys S. Allan

Keyword(s):

Immune System ◽

Cell Function ◽

Immune Cell ◽

Proliferating Cells ◽

Hematopoietic Stem ◽

Polycomb Repressive Complex 2 ◽

Current State ◽

Core Components ◽

And Function ◽

Cell Cycle Inhibitors

AbstractThe polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at least in part by repressing cell cycle inhibitors. At later stages of immune cell differentiation, EZH2 plays essential roles in humoral and cell-mediated adaptive immunity, as well as the maintenance of immune homeostasis. EZH2 is often overactive in cancers, through both gain-of-function mutations and over-expression, an observation that has led to the development and clinical testing of specific EZH2 inhibitors. Such inhibitors may also be of use in inflammatory and autoimmune settings, as EZH2 inhibition dampens the immune response. Here, we will review the current state of understanding of the roles for EZH2, and PRC2 more generally, in the development and function of the immune system.

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Effects of carotenoids on human immune function

Proceedings of The Nutrition Society ◽

10.1017/s0029665199000932 ◽

1999 ◽

Vol 58 (3) ◽

pp. 713-718 ◽

Cited By ~ 68

Author(s):

David A. Hughes

Keyword(s):

Immune Function ◽

Cell Function ◽

Immune Cell ◽

Antioxidant Properties ◽

The Elderly ◽

Causative Factor ◽

Epidemiological Studies ◽

Wide Range ◽

Β Carotene

Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, β-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that β-carotene may enhance immune cell function. Several human trials, using dietary β-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of β-carotene supplementation on lung cancer risk will be discussed.

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Immunotoxicological Effects of Jp-8 Jet Fuel Exposure

Toxicology and Industrial Health ◽

10.1177/074823379701300104 ◽

1997 ◽

Vol 13 (1) ◽

pp. 43-55 ◽

Cited By ~ 58

Author(s):

David T. Harris ◽

Debbie Sakiestewa ◽

Raymond F. Robledo ◽

Mark Witten

Keyword(s):

Immune System ◽

Immune Function ◽

Immune Cell ◽

Occupational Exposures ◽

The United States ◽

Jet Fuel ◽

Environmental Toxicants ◽

Immune Organ ◽

Toxicological Effects ◽

Exposed Individual

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed (3–5). Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (e.g., physiology, cardiology, respiratory, etc.); e.g., the immune system. Significant changes in immune consequences, even if short-lived, may have serious consequences for the exposed host that may impinge affect susceptibility to infectious agents. Major alterations in immune function that are long-lasting may result in an increased likelihood of development and/or progression of cancer, as well as autoimmune diseases. In the current study mice were exposed for 1h/day for 7 days to varying concentrations of aerosolized JP-8 jet fuel to simulate occupational exposures. Twenty-four hours after the last exposure the mice were analyzed for effects on their immune systems. It was observed that even at exposure concentrations as low as 100 mg/m3 detrimental effects on the immune system occurred. Decreases in viable immune cell numbers and immune organ weights were found. Jet fuel exposure resulted in losses of different immune cell subpopulations depending upon the immune organ being examined. Further, JP-8 exposure resulted in significantly decreased immune function, as analyzed by mitogenesis assays. Suppressed immune function could not be overcome by the addition of exogenous growth factors known to stimulate immune function. Thus, short-term, low concentration exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure, as effects were seen at concentrations of jet fuel that did not evidence change in other biological systems. Such changes may have significant effects on the health of the exposed individual.

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