CTLA-4 Signaling Regulates the Intensity of Hypersensitivity Responses to Food Antigens, but is Not Decisive in the Induction of Sensitization

Although food allergy has emerged as a major health problem, the mechanisms that are decisive in the development of sensitization to dietary Ag remain largely unknown. CTLA-4 signaling negatively regulates immune activation, and may play a crucial role in preventing induction and/or progression of sensitization to food Ag. To elucidate the role of CTLA-4 signaling in responses to food allergens, a murine model of peanut allergy was used. During oral exposure to peanut protein extract (PPE) together with the mucosal adjuvant cholera toxin (CT), which induces peanut allergy, CTLA-4 ligation was prevented using a CTLA-4 mAb. Additionally, the effect of inhibition of the CTLA-4 pathway on oral exposure to PPE in the absence of CT, which leads to unresponsiveness to peanut Ag, was explored. During sensitization, anti-CTLA-4 treatment considerably enhanced IgE responses to PPE and the peanut allergens, Ara h 1, Ara h 3, and Ara h 6, resulting in elevated mast cell degranulation upon an oral challenge. Remarkably, antagonizing CTLA-4 during exposure to PPE in the absence of CT resulted in significant induction of Th2 cytokines and an elevation in total serum IgE levels, but failed to induce allergen-specific IgE responses and mast cell degranulation upon a PPE challenge. These results indicate that CTLA-4 signaling is not the crucial factor in preventing sensitization to food allergens, but plays a pivotal role in regulating the intensity of a food allergic sensitization response. Furthermore, these data indicate that a profoundly Th2-biased cytokine environment is insufficient to induce allergic responses against dietary Ag

Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE). Subjects and methods: Serum samples (n = 41) obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). Results: 31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p < 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99-2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention. Conclusion: While this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants

The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment

Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow’s Milk Allergy

Cow’s milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release

The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment

Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow’s Milk Allergy

Cow’s milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release

Selenium-enriched soy protein has antioxidant potential via modulation of the NRF2-HO1 signaling pathway

Selenium (Se)-enriched proteins are an important dietary source of Se for humans; however, only a few Se-enriched proteins have been identified. In the present study, we tested for potential antioxidant activity by Se-enriched soy protein, both in vitro and in vivo. Se-enriched soy protein isolate (S-SPI) was shown to have a higher free radical scavenging ability compared to ordinary soy protein isolate (O-SPI). Furthermore, Caco-2 cell viability was improved by S-SPI at low doses, whereas O-SPI did not. In addition, S-SPI was shown to inhibit oxidative stress via modulation of the NRF2-HO1 signaling pathway, upregulating the expression of downstream antioxidant enzymes (GPx, SOD). To further study the antioxidant capacity of S-SPI, BALB/c female mice were given oral gavages with 0.8 mL of S-SPI or O-SPI (5 g/kg/d, 20 g/kg/d and 40 g/kg/d) or saline as control. Hepatic GPx and SOD activity increased with increasing S-SPI dosage, but not with O-SPI. Taken together, our results suggest that Se-enriched soy protein has a high antioxidant ability and may be used as a dietary supplement for people with oxidative dam-age-mediated diseases

Selenium-enriched soy protein has antioxidant potential via modulation of the NRF2-HO1 signaling pathway

Selenium (Se)-enriched proteins are an important dietary source of Se for humans; however, only a few Se-enriched proteins have been identified. In the present study, we tested for potential antioxidant activity by Se-enriched soy protein, both in vitro and in vivo. Se-enriched soy protein isolate (S-SPI) was shown to have a higher free radical scavenging ability compared to ordinary soy protein isolate (O-SPI). Furthermore, Caco-2 cell viability was improved by S-SPI at low doses, whereas O-SPI did not. In addition, S-SPI was shown to inhibit oxidative stress via modulation of the NRF2-HO1 signaling pathway, upregulating the expression of downstream antioxidant enzymes (GPx, SOD). To further study the antioxidant capacity of S-SPI, BALB/c female mice were given oral gavages with 0.8 mL of S-SPI or O-SPI (5 g/kg/d, 20 g/kg/d and 40 g/kg/d) or saline as control. Hepatic GPx and SOD activity increased with increasing S-SPI dosage, but not with O-SPI. Taken together, our results suggest that Se-enriched soy protein has a high antioxidant ability and may be used as a dietary supplement for people with oxidative dam-age-mediated diseases