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Dietary Regulation of Immunity.
Lee, AH, Dixit, VD
Immunity. 2020;(3):510-523
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Abstract
Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.
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Rheumatologists' perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets.
Misra, DP, Agarwal, V, Gasparyan, AY, Zimba, O
Clinical rheumatology. 2020;(7):2055-2062
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Abstract
The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren's syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still's disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.Key Points• Patients with coronavirus disease 19 (COVID-19) may have features mimicking rheumatic diseases, such as arthralgias, acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.
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Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin.
Jiang, Y, Tsoi, LC, Billi, AC, Ward, NL, Harms, PW, Zeng, C, Maverakis, E, Kahlenberg, JM, Gudjonsson, JE
JCI insight. 2020;(20)
Abstract
The skin serves as the primary interface between our body and the external environment and acts as a barrier against entry of physical agents, chemicals, and microbes. Keratinocytes make up the main cellular constitute of the outermost layer of the skin, contributing to the formation of the epidermis, and they are crucial for maintaining the integrity of this barrier. Beyond serving as a physical barrier component, keratinocytes actively participate in maintaining tissue homeostasis, shaping, amplifying, and regulating immune responses in skin. Keratinocytes act as sentinels, continuously monitoring changes in the environment, and, through microbial sensing, stretch, or other physical stimuli, can initiate a broad range of inflammatory responses via secretion of various cytokines, chemokines, and growth factors. This diverse function of keratinocytes contributes to the highly variable clinical manifestation of skin immune responses. In this Review, we highlight the highly diverse functions of epidermal keratinocytes and their contribution to various immune-mediated skin diseases.
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The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis.
de Almeida Brasiel, PG
Clinical nutrition ESPEN. 2020;:65-66
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Abstract
BACKGROUND & AIMS The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.
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Protein intake and amino acid supplementation regulate exercise recovery and performance through the modulation of mTOR, AMPK, FGF21, and immunity.
Torre-Villalvazo, I, Alemán-Escondrillas, G, Valle-Ríos, R, Noriega, LG
Nutrition research (New York, N.Y.). 2019;:1-17
Abstract
Exercise is considered to be the best approach to improve quality of life, and together with a healthy and adequate dietary pattern, exercise represents the best strategy to reduce the risk of chronic metabolic and inflammatory diseases, such as those related to obesity. The regularity and intensity of exercise is modulated at the molecular level in the skeletal muscle by two protein kinases, the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), which act as sensors of external stimuli, showing the energy status of muscular fibers. The mTOR pathway is activated by insulin and amino acid availability, and its metabolic actions culminate in increased protein synthesis and reduced autophagy, leading to an increase in muscle mass. In contrast, AMPK activation induces a transcriptional program aimed to increase the mitochondrial content in skeletal muscle, transforming fast-twitch glycolytic fibers to slow-twitch oxidative fibers and increasing resistance to fatigue. In addition, inadequate exercise training induces imbalance in the immune response, generating excessive inflammation and/or immunosuppression. The purpose of this review is to summarize recent studies that provide insight into dietary protein interventions and/or amino acid supplementation that may improve outcomes after exercise by modulating 1) mTOR and AMPK activation during early exercise recovery, leading to increased muscle protein synthesis or increased oxidative capacity; 2) undesirable inflammatory responses; and 3) fibroblast growth factor 21 (FGF21) levels that may have relevant implications in skeletal muscle metabolism, particularly during the exercise recovery and performance of obese subjects.
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Immune Function and Micronutrient Requirements Change over the Life Course.
Maggini, S, Pierre, A, Calder, PC
Nutrients. 2018;(10)
Abstract
As humans age, the risk and severity of infections vary in line with immune competence according to how the immune system develops, matures, and declines. Several factors influence the immune system and its competence, including nutrition. A bidirectional relationship among nutrition, infection and immunity exists: changes in one component affect the others. For example, distinct immune features present during each life stage may affect the type, prevalence, and severity of infections, while poor nutrition can compromise immune function and increase infection risk. Various micronutrients are essential for immunocompetence, particularly vitamins A, C, D, E, B2, B6, and B12, folic acid, iron, selenium, and zinc. Micronutrient deficiencies are a recognized global public health issue, and poor nutritional status predisposes to certain infections. Immune function may be improved by restoring deficient micronutrients to recommended levels, thereby increasing resistance to infection and supporting faster recovery when infected. Diet alone may be insufficient and tailored micronutrient supplementation based on specific age-related needs necessary. This review looks at immune considerations specific to each life stage, the consequent risk of infection, micronutrient requirements and deficiencies exhibited over the life course, and the available evidence regarding the effects of micronutrient supplementation on immune function and infection.
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The developing gut microbiota and its consequences for health.
Butel, MJ, Waligora-Dupriet, AJ, Wydau-Dematteis, S
Journal of developmental origins of health and disease. 2018;(6):590-597
Abstract
The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from the conception to the 2 years of life). The process of the gut microbiota establishment is included in this time window. Various perinatal determinants, such as cesarean section delivery, type of feeding, antibiotics treatment, gestational age or environment, can affect the pattern of bacterial colonization and result in dysbiosis. The alteration of the early bacterial gut pattern can persist over several months and may have long-lasting functional effects with an impact on disease risk later in life. As for example, early gut dysbiosis has been involved in allergic diseases and obesity occurrence. Besides, while it was thought that the fetus developed under sterile conditions, recent data suggested the presence of a microbiota in utero, particularly in the placenta. Even if the origin of this microbiota and its eventual transfer to the infant are nowadays unknown, this placental microbiota could trigger immune responses in the fetus and would program the infant's immune development during fetal life, earlier than previously considered. Moreover, several studies demonstrated a link between the composition of placental microbiota and some pathological conditions of the pregnancy. All these data show the evidence of relationships between the neonatal gut establishment and future health outcomes. Hence, the use of pre- and/or probiotics to prevent or repair any early dysbiosis is increasingly attractive to avoid long-term health consequences.
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From Infections to Anthropogenic Inflicted Pathologies: Involvement of Immune Balance.
Lee, F, Lawrence, DA
Journal of toxicology and environmental health. Part B, Critical reviews. 2018;(1):24-46
Abstract
A temporal trend can be seen in recent human history where the dominant causes of death have shifted from infectious to chronic diseases in industrialized societies. Human influences in the current "Anthropocene" epoch are exponentially impacting the environment and consequentially health. Changing ecological niches are suggested to have created health transitions expressed as modifications of immune balance from infections inflicting pathologies in the Holocene epoch (12,000 years ago) to human behaviors inflicting pathologies beginning in the Anthropocene epoch (300 years ago). A review of human immune health and adaptations responding to environmental (biological, chemical, physical, and psychological) stresses, which are influenced by social conditions, emphasize the involvement of fluctuations in immune cell subsets affecting influential gene-environment interactions. The literature from a variety of fields (anthropological, immunological, and environmental) is incorporated to present an expanded perspective on shifts in diseases within the context of immune balance and function and environmental immunology. The influences between historical and contemporary human ecology are examined in relation to human immunity. Several examples of shifts in human physiology and immunity support the premise that increased incidences of chronic diseases are a consequence of human modification of environment and lifestyle. Although the development of better health care and a broader understanding of human health have helped with better life quality and expectancy, the transition of morbidity and mortality rates from infections to chronic diseases is a cause for concern. Combinations of environmental stressors/pollutants and human behaviors and conditions are modulating the immune-neuroendocrine network, which compromises health benefits.
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The Microbiotic Highway to Health-New Perspective on Food Structure, Gut Microbiota, and Host Inflammation.
Hansen, NW, Sams, A
Nutrients. 2018;(11)
Abstract
This review provides evidence that not only the content of nutrients but indeed the structural organization of nutrients is a major determinant of human health. The gut microbiota provides nutrients for the host by digesting food structures otherwise indigestible by human enzymes, thereby simultaneously harvesting energy and delivering nutrients and metabolites for the nutritional and biological benefit of the host. Microbiota-derived nutrients, metabolites, and antigens promote the development and function of the host immune system both directly by activating cells of the adaptive and innate immune system and indirectly by sustaining release of monosaccharides, stimulating intestinal receptors and secreting gut hormones. Multiple indirect microbiota-dependent biological responses contribute to glucose homeostasis, which prevents hyperglycemia-induced inflammatory conditions. The composition and function of the gut microbiota vary between individuals and whereas dietary habits influence the gut microbiota, the gut microbiota influences both the nutritional and biological homeostasis of the host. A healthy gut microbiota requires the presence of beneficial microbiotic species as well as vital food structures to ensure appropriate feeding of the microbiota. This review focuses on the impact of plant-based food structures, the "fiber-encapsulated nutrient formulation", and on the direct and indirect mechanisms by which the gut microbiota participate in host immune function.
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10.
The Transcription Factor EB Links Cellular Stress to the Immune Response
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Nabar, NR, Kehrl, JH
The Yale journal of biology and medicine. 2017;(2):301-315
Abstract
The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB's function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation.