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11 pages, 1050 KiB

Open AccessArticle

Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

by Emina Halilbasic, Elisabeth Fuerst, Denise Heiden, Lukasz Japtok, Susanne C. Diesner, Michael Trauner, Askin Kulu, Peter Jaksch, Konrad Hoetzenecker, Burkhard Kleuser, Lili Kazemi-Shirazi and Eva Untersmayr

Nutrients 2020, 12(3), 765; https://doi.org/10.3390/nu12030765 - 14 Mar 2020

Cited by 8 | Viewed by 3122

Abstract

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels [...] Read more.

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in ΔF508-homozygous compared to ΔF508-heterozygous CF patients (p = 0.038), accompanied by higher levels of HDL in ΔF508-heterozygous patients. Gastrointestinal symptoms were more common in ΔF508 heterozygotes compared to ΔF508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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16 pages, 2631 KiB

Open AccessArticle

Alliin, An Allium sativum Nutraceutical, Reduces Metaflammation Markers in DIO Mice

by Marina A. Sánchez-Sánchez, Adelaida Sara Minia Zepeda-Morales, Lucrecia Carrera-Quintanar, Juan Manuel Viveros-Paredes, Noel Noé Franco-Arroyo, Marisol Godínez-Rubí, Daniel Ortuño-Sahagun and Rocío Ivette López-Roa

Nutrients 2020, 12(3), 624; https://doi.org/10.3390/nu12030624 - 27 Feb 2020

Cited by 19 | Viewed by 4539

Abstract

Obesity generates a chronic low-grade inflammatory state which promotes oxidative stress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has been shown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect on metabolic parameters and [...] Read more.

Obesity generates a chronic low-grade inflammatory state which promotes oxidative stress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has been shown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect on metabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD and with obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.5 weeks (15 mg/kg) did not affect body weight, but significantly improved insulin sensitivity and glucose tolerance, both evaluated through a blood glucose monitoring system. Once alliin treatment was completed, serum, adipose tissue, and organs of interest related to metabolism were removed for further analysis. We observed that alliin significantly decreased the size of adipocytes from epididymal adipose tissue, evaluated via microscopy. A decrease in gene expression and serum protein levels of the adipocytokines leptin and resistin, as well as decreased serum IL-6 concentration, were detected by qRT-PCR and ELISA, respectively. It did not, however, affect mRNA expression of antioxidant enzymes in the liver. Taken altogether, these results indicate that treatment with alliin reduces metaflammation markers in DIO mice and improves some metabolic parameters without affecting others. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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20 pages, 3336 KiB

Open AccessArticle

Walnut Polyphenol Extract Protects against Malathion- and Chlorpyrifos-Induced Immunotoxicity by Modulating TLRx-NOX-ROS

by Yue Zhao, Chang Fan, Ao Zhang, Yue Zhang, Fengjun Wang, Qiang Weng and Meiyu Xu

Nutrients 2020, 12(3), 616; https://doi.org/10.3390/nu12030616 - 27 Feb 2020

Cited by 19 | Viewed by 3144

Abstract

Malathion (MT) and chlorpyrifos (CPF) are immunotoxic organophosphate pesticides that are used extensively in agriculture worldwide. Dietary polyphenols protect against a variety of toxins. In this study, walnut polyphenol extract (WPE) prevents MT- or CPF-induced toxicity to splenic lymphocytes in vitro. WPE promotes [...] Read more.

Malathion (MT) and chlorpyrifos (CPF) are immunotoxic organophosphate pesticides that are used extensively in agriculture worldwide. Dietary polyphenols protect against a variety of toxins. In this study, walnut polyphenol extract (WPE) prevents MT- or CPF-induced toxicity to splenic lymphocytes in vitro. WPE promotes the proliferation of MT-exposed splenocytes, as indicated by increases in the proportions of splenic T-lymphocyte subpopulations (CD3⁺, CD4⁺, and CD8⁺ T cells) and levels of T-cell-related cytokines interleukin (IL)-2, interferon-γ, IL-4, and granzyme B, and decreases the apoptosis-associated proteins Bax and p53. WPE also significantly enhances the proliferation of CPF-exposed splenic B lymphocytes (CD19⁺ B cells) and levels of the B-cell-related cytokine IL-6, leading to decreases of the apoptosis-associated proteins Bax and p53. These effects are related to reduced production of reactive oxygen species (ROS), as evidenced by normalized hydroxyl radical (•OH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione (GSH) levels, which are associated with decreased expression of NADPH oxidase 2 (NOX2) and dual oxidase 1 (DUOX1). WPE inhibits the production of ROS and expression of NOX by regulating toll-like receptors 4 and 7 in MT- and CPF-exposed splenic lymphocytes. In conclusion, WPE protects against MT- or CPF-mediated immunotoxicity and inhibits oxidative damage by modulating toll-like receptor (TLR)x-NOX-ROS. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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16 pages, 6244 KiB

Open AccessArticle

Nutritional and Pharmacological Targeting of the Calcium-Sensing Receptor Influences Chemically Induced Colitis in Mice

by Taha Elajnaf, Luca Iamartino, Ildiko Mesteri, Christian Müller, Marcella Bassetto, Teresa Manhardt, Sabina Baumgartner-Parzer, Enikö Kallay and Martin Schepelmann

Nutrients 2019, 11(12), 3072; https://doi.org/10.3390/nu11123072 - 16 Dec 2019

Cited by 14 | Viewed by 4918

Abstract

The calcium-sensing receptor (CaSR) is the main regulator of extracellular Ca²⁺ homeostasis. It has diverse functions in different tissues, including the intestines. Intestine-specific knockout of the CaSR renders mice more susceptible to dextran sulphate sodium (DSS)-induced colitis. To test our hypothesis that [...] Read more.

The calcium-sensing receptor (CaSR) is the main regulator of extracellular Ca²⁺ homeostasis. It has diverse functions in different tissues, including the intestines. Intestine-specific knockout of the CaSR renders mice more susceptible to dextran sulphate sodium (DSS)-induced colitis. To test our hypothesis that the CaSR reduces intestinal inflammation, we assessed the effects of nutritional and pharmacological agonists of the CaSR in a colitis model. We treated female Balb/C mice with dietary calcium and protein (nutritional agonists of the CaSR) or pharmacological CaSR modulators (the agonists cinacalcet and GSK3004774, and the antagonist NPS-2143; 10 mg/kg), then induced colitis with DSS. The high-protein diet had a strong pro-inflammatory effect—it shortened the colons (5.3 ± 0.1 cm vs. 6.1 ± 0.2 cm normal diet, p < 0.05), lowered mucin expression and upregulated pro-inflammatory cytokines, such as interferon-γ, (4.2-fold, p < 0.05) compared with the normal diet. Cinacalcet reduced mucin expression, which coincided with an increase in tumor necrosis factor-α (4.4-fold, p < 0.05) and IL-6 (4.9-fold, p < 0.05) in the plasma, compared with vehicle. The CaSR antagonist, NPS-2143, significantly reduced the cumulative inflammation score compared with the vehicle control (35.3 ± 19.1 vs. 21.9 ± 14.3 area under the curve, p < 0.05) and reduced infiltration of inflammatory cells. While dietary modulation of the CaSR had no beneficial effects, pharmacological inhibition of the CaSR may have the potential of a novel add-on therapy in the treatment of inflammatory bowel diseases. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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15 pages, 1499 KiB

Open AccessArticle

Immune Effects of the Nitrated Food Allergen Beta-Lactoglobulin in an Experimental Food Allergy Model

by Anna S. Ondracek, Denise Heiden, Gertie J. Oostingh, Elisabeth Fuerst, Judit Fazekas-Singer, Cornelia Bergmayr, Johanna Rohrhofer, Erika Jensen-Jarolim, Albert Duschl and Eva Untersmayr

Nutrients 2019, 11(10), 2463; https://doi.org/10.3390/nu11102463 - 15 Oct 2019

Cited by 5 | Viewed by 3105

Abstract

Food proteins may get nitrated by various exogenous or endogenous mechanisms. As individuals might get recurrently exposed to nitrated proteins via daily diet, we aimed to investigate the effect of repeatedly ingested nitrated food proteins on the subsequent immune response in non-allergic and [...] Read more.

Food proteins may get nitrated by various exogenous or endogenous mechanisms. As individuals might get recurrently exposed to nitrated proteins via daily diet, we aimed to investigate the effect of repeatedly ingested nitrated food proteins on the subsequent immune response in non-allergic and allergic mice using the milk allergen beta-lactoglobulin (BLG) as model food protein in a mouse model. Evaluating the presence of nitrated proteins in food, we could detect 3-nitrotyrosine (3-NT) in extracts of different foods and in stomach content extracts of non-allergic mice under physiological conditions. Chemically nitrated BLG (BLGn) exhibited enhanced susceptibility to degradation in simulated gastric fluid experiments compared to untreated BLG (BLGu). Gavage of BLGn to non-allergic animals increased interferon-γ and interleukin-10 release of stimulated spleen cells and led to the formation of BLG-specific serum IgA. Allergic mice receiving three oral gavages of BLGn had higher levels of mouse mast cell protease-1 (mMCP-1) compared to allergic mice receiving BLGu. Regardless of the preceding immune status, non-allergic or allergic, repeatedly ingested nitrated food proteins seem to considerably influence the subsequent immune response. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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22 pages, 2909 KiB

Open AccessArticle

Leptin and EGF Supplementation Enhance the Immune System Maturation in Preterm Suckling Rats

by Blanca Grases-Pintó, Paulina Torres-Castro, Lidia Marín-Morote, Mar Abril-Gil, Margarida Castell, María J. Rodríguez-Lagunas, Francisco J. Pérez-Cano and Àngels Franch

Nutrients 2019, 11(10), 2380; https://doi.org/10.3390/nu11102380 - 06 Oct 2019

Cited by 10 | Viewed by 3415

Abstract

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system’s maturation in early life. However, studies on the [...] Read more.

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system’s maturation in early life. However, studies on the immunoregulatory activity in preterm neonates are practically nonexistent. The aim of the present study was to determine whether a nutritional supplementation in early life with leptin or epidermal growth factor (EGF) was able to promote the maturation of the systemic and intestinal immune system in preterm conditions. For this purpose, premature rats were daily supplemented by oral gavage with leptin or EGF. Term and Preterm groups receiving vehicle were used as controls. Preterm rats showed deficiencies compared to full-term ones, such as lower body weights, erythrocyte counts, plasma IgG and IgM concentrations and B cell percentages, and higher values of Th and Tc TCRαβ⁺ cells in mesenteric lymph nodes, and intestinal permeability, among others. However, leptin and EGF supplementation were able to revert some of these deficiencies and to improve the premature immune system’s development. These results suggest that leptin and EGF are involved in enhancing the maturation of the systemic and intestinal immune system in preterm conditions. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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10 pages, 464 KiB

Open AccessArticle

Fibre Intake Is Independently Associated with Increased Circulating Interleukin-22 in Individuals with Metabolic Syndrome

by Luciana Torquati, Jeff S. Coombes, Lydia Murray, Sumaira Z. Hasnain, Alistair R. Mallard, Michael A. McGuckin, Robert G. Fassett, Ilaria Croci and Joyce S. Ramos

Nutrients 2019, 11(4), 815; https://doi.org/10.3390/nu11040815 - 11 Apr 2019

Cited by 5 | Viewed by 4930

Abstract

The positive effects of dietary fibre on gut barrier function and inflammation have not been completely elucidated. Mice studies show gut barrier disruption and diet-induced insulin resistance can be alleviated by cytokine interleukin-22 (IL-22). However, little is known about IL-22 in humans and [...] Read more.

The positive effects of dietary fibre on gut barrier function and inflammation have not been completely elucidated. Mice studies show gut barrier disruption and diet-induced insulin resistance can be alleviated by cytokine interleukin-22 (IL-22). However, little is known about IL-22 in humans and its association with gut-beneficial nutrients like fibre. We investigated whether fibre intake was associated with circulating levels of IL-22 in 48 participants with metabolic syndrome (MetS). Bivariate analysis was used to explore associations between circulating IL-22, fibre intake, MetS factors, body composition, and cardiorespiratory fitness (peak oxygen uptake,

\dot{V}

O_2peak). Hierarchical multiple regression (HMR) was used to test the independent association of fibre intake with circulating IL-22, adjusting for variables correlated with IL-22. Circulating IL-22 was positively associated with fibre intake (r_s = 0.393, p < 0.006). The HMR-adjusted model explained 40% of circulating IL-22 variability, and fibre intake significantly improved the prediction model by 8.4% (p < 0.022). Participants with fibre intake above median intake of 21.5 g/day had a significantly higher circulating IL-22 than the lower intake group (308.3 ± 454.4 vs. 69.0 ± 106.4 pg/mL, p < 0.019). Fibre intake is independently associated with increased circulating IL-22 in individuals with MetS. Findings warrant further investigations to evaluate whether changes in dietary fibre intake alter circulating IL-22, and its effects on health outcomes. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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17 pages, 1636 KiB

Open AccessArticle

Protective Effect of Hesperidin on the Oxidative Stress Induced by an Exhausting Exercise in Intensively Trained Rats

by Sheila Estruel-Amades, Malén Massot-Cladera, Pau Garcia-Cerdà, Francisco J. Pérez-Cano, Àngels Franch, Margarida Castell and Mariona Camps-Bossacoma

Nutrients 2019, 11(4), 783; https://doi.org/10.3390/nu11040783 - 04 Apr 2019

Cited by 51 | Viewed by 4864

Abstract

Intensive exercise can lead to oxidative stress, which can be particularly deleterious for lymphoid tissues. Hesperidin has demonstrated its antioxidant activity, but few studies focus on its influence on intensive training. The aim of this study was to assess the impact of hesperidin [...] Read more.

Intensive exercise can lead to oxidative stress, which can be particularly deleterious for lymphoid tissues. Hesperidin has demonstrated its antioxidant activity, but few studies focus on its influence on intensive training. The aim of this study was to assess the impact of hesperidin on the oxidant/antioxidant status of lymphoid tissues after an intensive training program. Wistar rats were trained for five weeks (five days per week), including two exhaustion tests plus three trainings per week. During this period, animals were orally administrated with 200 mg/kg of hesperidin or vehicle (three days per week). The oxidative status was determined before, immediately after and 24 h after an additional exhaustion test. The production of reactive oxygen species (ROS) by peritoneal macrophages, superoxide dismutase (SOD) and catalase activities in spleen, thymus and liver, and hepatic glutathione peroxidase activity (GPx) were assessed. Hesperidin prevented an increase in ROS production induced by the additional exhaustion test. Likewise, hesperidin avoided a decrease in SOD and catalase activities in the thymus and spleen that was found after the additional exhaustion test. The antioxidant effects of hesperidin were associated with a higher performance in the assessed training model. These results suggest that hesperidin, acting as an antioxidant, can prevent oxidative stress induced by exercise and improve exercise performance. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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Review

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15 pages, 547 KiB

Open AccessReview

Nutrition and the Immune System: A Complicated Tango

by Carina Venter, Stefanie Eyerich, Tara Sarin and Kevin C. Klatt

Nutrients 2020, 12(3), 818; https://doi.org/10.3390/nu12030818 - 19 Mar 2020

Cited by 114 | Viewed by 23505

Abstract

Enthusiasm exists for the potential of diet to impact the immune system, prevent disease and its therapeutic potential. Herein, we describe the challenge to nutrition scientists in defining this relationship through case studies of diets and nutrients in the context of allergic and [...] Read more.

Enthusiasm exists for the potential of diet to impact the immune system, prevent disease and its therapeutic potential. Herein, we describe the challenge to nutrition scientists in defining this relationship through case studies of diets and nutrients in the context of allergic and autoimmune diseases. Moderate-quality evidence exists from both human intervention and observational studies to suggest that diet and individual nutrients can influence systemic markers of immune function and inflammation; numerous challenges exist for demonstrating the impact of defined diets and nutrient interventions on clearly influencing immune-mediated-clinical disease endpoints. A growing body of evidence suggests that further consideration of dietary patterns, immune system and gut microbiome composition and function, and subsequent epigenetic modifications are needed to improve our understanding of diet–immune system interactions. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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17 pages, 1604 KiB

Open AccessReview

Physical Activity and Diet Shape the Immune System during Aging

by Christopher Weyh, Karsten Krüger and Barbara Strasser

Nutrients 2020, 12(3), 622; https://doi.org/10.3390/nu12030622 - 28 Feb 2020

Cited by 94 | Viewed by 30924

Abstract

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of [...] Read more.

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of latent viruses, decreased vaccine efficacy, and an increased prevalence of autoimmunity and cancer. Physiologically, the immune system has some adaptive strategies to cope with aging, while in some settings, maladaptive responses aggravate the speed of aging and morbidity. While a lack of physical activity, decreased muscle mass, and poor nutritional status facilitate immunosenescence and inflammaging, lifestyle factors such as exercise and dietary habits affect immune aging positively. This review will discuss the relevance and mechanisms of immunoprotection through physical activity and specific exercise interventions. In the second part, we will focus on the effect of dietary interventions through the supplementation of the essential amino acid tryptophan, n-3 polyunsaturated fatty acids, and probiotics (with a special focus on the kynurenine pathway). Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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52 pages, 3094 KiB

Open AccessReview

The Influence of Dietary Fatty Acids on Immune Responses

by Urszula Radzikowska, Arturo O. Rinaldi, Zeynep Çelebi Sözener, Dilara Karaguzel, Marzena Wojcik, Katarzyna Cypryk, Mübeccel Akdis, Cezmi A. Akdis and Milena Sokolowska

Nutrients 2019, 11(12), 2990; https://doi.org/10.3390/nu11122990 - 06 Dec 2019

Cited by 172 | Viewed by 14953

Abstract

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and [...] Read more.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as n-6/n-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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14 pages, 1376 KiB

Open AccessReview

The Secrets of the Mediterranean Diet. Does [Only] Olive Oil Matter?

by Alessandra Mazzocchi, Ludovica Leone, Carlo Agostoni and Isabella Pali-Schöll

Nutrients 2019, 11(12), 2941; https://doi.org/10.3390/nu11122941 - 03 Dec 2019

Cited by 152 | Viewed by 22552

Abstract

Diet plays a key role in the maintenance and optimal functioning of immune cells. The Mediterranean dietary pattern is an example of a prudent choice of lifestyle and scientifically accepted to help preserve human health by protecting against major chronic and inflammatory diseases. [...] Read more.

Diet plays a key role in the maintenance and optimal functioning of immune cells. The Mediterranean dietary pattern is an example of a prudent choice of lifestyle and scientifically accepted to help preserve human health by protecting against major chronic and inflammatory diseases. Mediterranean diets (MedDiets) are characteristically high in the consumption of fruits, vegetables and salad, bread and whole grain cereals, potatoes, legumes/beans, nuts, and seeds. Their common central feature is the usage of olive oil as the main source of fat. The health benefits attributed to olive oil are specifically related to extra virgin olive oil (EVOO) intake with its high nutritional quality and multiple positive effects on health. Overall, MedDiets have direct (mono-unsaturated fatty acids (MUFAs), tocopherols, polyphenols) and indirect (low saturated fats, well-balanced linoleic/alpha linolenic acid) effects on the immune system and inflammatory responses. In the present paper, we summarize the current knowledge on the effect of olive oil per se and MedDiets generally on immune-mediated and inflammatory diseases, such as coronary heart disease (CHD)/cardiovascular diseases (CVD), obesity, type-2 diabetes, cancer, asthma, and allergies. Full article

(This article belongs to the Special Issue Immunomodulation and Nutrition)

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