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1.
The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders.
Arts, RJW, Joosten, LAB, Netea, MG
Frontiers in immunology. 2018;:298
Abstract
During induction of trained immunity, monocytes and macrophages undergo a functional and transcriptional reprogramming toward increased activation. Important rewiring of cellular metabolism of the myeloid cells takes place during induction of trained immunity, including a shift toward glycolysis induced through the mTOR pathway, as well as glutaminolysis and cholesterol synthesis. Subsequently, this leads to modulation of the function of epigenetic enzymes, resulting in important changes in chromatin architecture that enables increased gene transcription. However, in addition to the beneficial effects of trained immunity as a host defense mechanism, we hypothesize that trained immunity also plays a deleterious role in the induction and/or maintenance of autoimmune and autoinflammatory diseases if inappropriately activated.
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2.
How to predict and improve prognosis of food allergy.
Dahdah, L, Pecora, V, Riccardi, C, Fierro, V, Valluzzi, R, Mennini, M
Current opinion in allergy and clinical immunology. 2018;(3):228-233
Abstract
PURPOSE OF REVIEW The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up. RECENT FINDINGS Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature. SUMMARY A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.
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3.
Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.
Spanaki, AM, Tavladaki, T, Dimitriou, H, Kozlov, AV, Duvigneau, JC, Meleti, E, Weidinger, A, Papakonstantinou, E, Briassoulis, G
JPEN. Journal of parenteral and enteral nutrition. 2018;(6):1061-1074
Abstract
BACKGROUND Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (p<0.05); TBARS and VO2 were independently associated with organ failure (p<0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (p<0.05). CONCLUSIONS A pattern of early longitudinal induction of metabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.
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4.
Inflammaging: a new immune-metabolic viewpoint for age-related diseases.
Franceschi, C, Garagnani, P, Parini, P, Giuliani, C, Santoro, A
Nature reviews. Endocrinology. 2018;(10):576-590
Abstract
Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
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5.
Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis.
Muszynski, JA, Nofziger, R, Moore-Clingenpeel, M, Greathouse, K, Anglim, L, Steele, L, Hensley, J, Hanson-Huber, L, Nateri, J, Ramilo, O, et al
American journal of respiratory and critical care medicine. 2018;(3):361-369
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Abstract
RATIONALE Late immune suppression is associated with nosocomial infection and mortality in adults and children with sepsis. Relationships between early immune suppression and outcomes in children with sepsis remain unclear. OBJECTIVES Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis or septic shock. METHODS Children younger than 18 years of age meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy control subjects were sampled once. Innate immune function was quantified by whole blood ex vivo LPS-induced TNF-α (tumor necrosis factor-α) production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN-γ production capacity. MEASUREMENTS AND MAIN RESULTS One hundred two children with sepsis and 35 healthy children were enrolled. Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-α production (P < 0.0001) and lower phytohemagglutinin-induced IFN-γ production (P < 0.0001). Among children with sepsis, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction syndrome and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased multiple organ dysfunction syndrome days (adjusted relative risk, 1.2; 95% confidence interval, 1.03-1.5) and organ dysfunction days (adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSIONS Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early innate and adaptive immune suppression are associated with longer durations of organ dysfunction and may be useful markers to help guide future investigations of immunomodulatory therapies in children with sepsis.
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Innate Immune Cell Suppression and the Link With Secondary Lung Bacterial Pneumonia.
Morgan, DJ, Casulli, J, Chew, C, Connolly, E, Lui, S, Brand, OJ, Rahman, R, Jagger, C, Hussell, T
Frontiers in immunology. 2018;:2943
Abstract
Secondary infections arise as a consequence of previous or concurrent conditions and occur in the community or in the hospital setting. The events allowing secondary infections to gain a foothold have been studied for many years and include poor nutrition, anxiety, mental health issues, underlying chronic diseases, resolution of acute inflammation, primary immune deficiencies, and immune suppression by infection or medication. Children, the elderly and the ill are particularly susceptible. This review is concerned with secondary bacterial infections of the lung that occur following viral infection. Using influenza virus infection as an example, with comparisons to rhinovirus and respiratory syncytial virus infection, we will update and review defective bacterial innate immunity and also highlight areas for potential new investigation. It is currently estimated that one in 16 National Health Service (NHS) hospital patients develop an infection, the most common being pneumonia, lower respiratory tract infections, urinary tract infections and infection of surgical sites. The continued drive to understand the mechanisms of why secondary infections arise is therefore of key importance.
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Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial.
Dolati, S, Aghebati-Maleki, L, Ahmadi, M, Marofi, F, Babaloo, Z, Ayramloo, H, Jafarisavari, Z, Oskouei, H, Afkham, A, Younesi, V, et al
Journal of cellular physiology. 2018;(7):5222-5230
Abstract
In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing-remitting multiple sclerosis (RRMS). We intended to investigate the expression pattern of these miRNAs in experimental settings in vivo. The expression levels of the selected 27 miRNAs known to be involved in the regulation of immune responses were analyzed in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were investigated by quantitative PCR (qPCR) at baseline and after 6 months of nanocurcumin therapy. Our data revealed that the expression of a number of microRNAs including miR-16, miR-17-92, miR-27, miR-29b, miR-126, miR-128, miR-132, miR-155, miR-326, miR-550, miR-15a, miR-19b, miR-106b, miR-320a, miR-363, miR-31, miR-150, and miR-340 is regulated by nanocurcumin. The results of the current work indicate that nanocurcumin is able to restore the expression pattern of dysregulated miRNAs in MS patients. We discovered that some miRNAs are deregulated in untreated patients compared with healthy controls and nanocurcumin-treated patients. This is a new finding that might represent the potential contribution of these miRNAs to MS pathogenesis. Taken together, these data provide novel insights into miRNA-dependent regulation of the function of B and T cells in MS disease and enrich our understanding of the effects mediated by a therapeutic approach that targets B and T cells.
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Nutritional Modulation of Innate Immunity: The Fat-Bile-Gut Connection.
Chevre, R, Silvestre-Roig, C, Soehnlein, O
Trends in endocrinology and metabolism: TEM. 2018;(10):686-698
Abstract
Altered nutritional behavior in Western societies has unleashed numerous metabolic disorders, intimately linked to profound disruptions of the immune system. Here we summarize how nutrition modulates innate immunity. We outline recent findings regarding nutrient signaling and we particularly focus on the collateral impact of nutrition on the microbiome and on the bile acid (BA) pool. We discuss how the integration of postprandial signals by the gut microbiota, along with the absorption routes of metabolites, differentially affects immune niches to orchestrate immune responses. Finally, we discuss the potential consequences of these signals in the light of trained immunity. A better understanding of nutrition signaling will permit the optimization of therapeutic and dietary strategies against the arising immune disorders.
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High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response.
Haghikia, A, Landmesser, U
Cardiology clinics. 2018;(2):317-327
Abstract
The focus in studies of high-density lipoproteins was on their capacity to remove excess cholesterol and deliver it to the liver. Other functions and vascular effects have been described. Clinical trials and translational/genetic studies have led to a refined understanding of the role of high-density lipoprotein; it is likely not a causal cardiovascular risk factor. In healthy subjects, it limits lipid oxidation, protects endothelial cell functions/integrity, and exerts antiinflammatory/antiapoptotic effects. In patients with coronary disease or diabetes, it undergoes modifications/remodeling, resulting in dysfunctional high-density lipoprotein. We summarize recent findings about the regulation of its function and discuss the clinical implications.
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10.
Adipocytokine Involvement in Innate Immune Mechanisms.
Żelechowska, P, Kozłowska, E, Pastwińska, J, Agier, J, Brzezińska-Błaszczyk, E
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2018;(12):527-538
Abstract
The innate immune response is defined as an immensely complex and sophisticated process aimed at defending the organism against any disturbance in the body homeostasis, including invading pathogens. It requires a close cooperation of a vast amount of different cell types, recognized as inflammatory migrating cells, as well as stationary cells that form tissues. Moreover, innate immune mechanisms require an efficient functioning of various humoral components that exert a significant impact on physiological and pathological processes. Apart from commonly mentioned humoral factors, this group also includes a family of proteins known as adipocytokines that may act as pro- or anti-inflammatory agents or act both ways. Leptin, predominantly characterized as a proinflammatory adipokine, plays a crucial role in endothelium remodeling and regulation, as well as in cell survival and production of numerous cytokines. Adiponectin, similar to leptin, acts on the endothelial cells and the phagocytic properties of immune cells; however, it exerts an anti-inflammatory impact. Resistin has a documented role in the control of angiogenesis and stimulation of proinflammatory mediator generation and release. Furthermore, there are adipokines, ie, visfatin and chemerin, whose participation in the inflammatory processes is ambiguous. This review focuses on the current knowledge on the extensive role of selected adipokines in innate immune response.