Exposure to Deoxynivalenol During Pregnancy and Lactation Enhances Food Allergy and Reduces Vaccine Responsiveness in the Offspring in a Mouse Model

Deoxynivalenol (DON), a highly prevalent contaminant of grain-based products, is known to induce reproductive- and immunotoxicities. Considering the importance of immune development in early life, the present study investigated the effects of perinatal DON exposure on allergy development and vaccine responsiveness in the offspring. Pregnant mice received control or DON-contaminated diets (12.5 mg/kg diet) during pregnancy and lactation. After weaning, female offspring were sensitized to ovalbumin (OVA) by oral administration of OVA with cholera toxin (CT). Male offspring were injected with Influvac vaccine. OVA-specific acute allergic skin response (ASR) in females and vaccine-specific delayed-type hypersensitivity (DTH) in males were measured upon intradermal antigen challenge. Immune cell populations in spleen and antigen-specific plasma immunoglobulins were analyzed. In female CT+OVA-sensitized offspring of DON-exposed mothers ASR and OVA-specific plasma immunoglobulins were significantly higher, compared to the female offspring of control mothers. In vaccinated male offspring of DON-exposed mothers DTH and vaccine-specific antibody levels were significantly lower, compared to the male offspring of control mothers. In both models a significant reduction in regulatory T cells, Tbet+ Th1 cells and Th1-related cytokine production of the offspring of DON-exposed mothers was observed. In conclusion, early life dietary exposure to DON can adversely influence immune development in the offspring. Consequently, the immune system of the offspring may be skewed towards an imbalanced state, resulting in an increased allergic immune response to food allergens and a decreased immune response to vaccination against influenza virus in these models.

Impact of Anemia on the School Performance of Students at a Public School in Ceará

Anemia is defined as a condition in which hemoglobin levels are below the normal range. Among children and adolescents, iron deficiency is responsible for most cases. Iron is an essential compound for the production of red blood cells and transportation of oxygen, as well as for the integration of the enzymatic systems of different tissues. Patients with iron deficiency anemia may have impaired cognitive, physical and immune development, thus increasing the risk of infections and even death. This is a cross-sectional study to analyze the prevalence of anemia and its impact on school and nutritional performance among elementary school adolescents aged between 10 and 14 years from May 2019 to October 2019.

Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model

Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.

Effects of crude oil on juvenile threespine stickleback somatic and immune development

Aquatic oil spills have resounding effects on surrounding ecosystems, and thus significant resources are committed to oil spill responses to remove the oil from the environment as quickly as possible. Oil has immunotoxic effects and may be particularly harmful to larval and juvenile fish as it can cause a number of developmental defects and stunt growth. In spite of significant efforts to clean oil, it is unclear whether larval and juvenile fish can recover from the effects of oil and no work has been done on the effect crude oil has on developing threespine stickleback (Gasterosteus aculeatus) fish. Threespine stickleback are a ubiquitous sentinel species in the northern hemisphere and are an important food source for many larger, economically valuable fish. As fish with fully marine, anadromous, and freshwater populations, stickleback are exposed to oil in a variety of aquatic environments. We hypothesized that oil exposure would suppress both growth and immunity of developing stickleback, but that fish health could be recovered by removal of the crude oil. Fish were exposed to Alaska North Slope crude oil and then were moved to water without crude oil for two weeks (depuration). Measurements of growth and immunity were taken before and after the depuration. We found that crude oil effected different developmental pathways independently, significantly impacting some but not others. This is the first study to examine the effect crude oil has on early stages of stickleback development, and that stickleback fish are unable to recover from exposure after being transferred to clean water for two-weeks, suggesting larval/juvenile stickleback exposed to crude oil need longer than two-weeks to recover if they are able to recover at all.

Proper Immune Response Depends on Early Exposure to Gut Microbiota in Broiler Chicks

The successional changes in the early intestinal microbiota occur concomitantly with the development, expansion, and education of the mucosal immune system. Although great attention of researchers has been focused on understanding the linkage between microbiota and immune functions, many essential details of the symbiotic relationship between the intestinal pioneer microbiota and the avian immune system remain to be discovered. This study was conducted to understand the impact of different early life intestinal colonizers on innate and adaptive immune processes in chicks and further identify immune-associated proteins expressed in the intestinal tissue. To accomplish it, we performed an in ovo application of two apathogenic Enterobacteriaceae isolates and lactic acid bacteria (L) to determine their influences on the intestinal proteome profile of broilers at the day of hatch (DOH) and at 10 days old. The results indicated that there were predicted biological functions of L-treated chicks associated with the activation and balanced function of the innate and adaptive immune systems. At the same time, the Enterobacteriaceae-exposed birds presented dysregulated immunological mechanisms or downregulated processes related to immune development. Those findings suggested that a proper immune function was dependent on specific gut microbiota exposure, in which the prenatal probiotic application may have favored the fitting programming of immune functions in chicks.

Defining the Role of Nuclear Factor (NF)-κB p105 Subunit in Human Macrophage by Transcriptomic Analysis of NFKB1 Knockout THP1 Cells

Since its discovery over 30 years ago the NF-ĸB family of transcription factors has gained the status of master regulator of the immune response. Much of what we understand of the role of NF-ĸB in immune development, homeostasis and inflammation comes from studies of mice null for specific NF-ĸB subunit encoding genes. The role of inflammation in diseases that affect a majority of individuals with health problems globally further establishes NF-ĸB as an important pathogenic factor. More recently, genomic sequencing has revealed loss of function mutations in the NFKB1 gene as the most common monogenic cause of common variable immunodeficiencies in Europeans. NFKB1 encodes the p105 subunit of NF-ĸB which is processed to generate the NF-ĸB p50 subunit. NFKB1 is the most highly expressed transcription factor in macrophages, key cellular drivers of inflammation and immunity. Although a key role for NFKB1 in the control of the immune system is apparent from Nfkb1-/- mouse studies, we know relatively little of the role of NFKB1 in regulating human macrophage responses. In this study we use the THP1 monocyte cell line and CRISPR/Cas9 gene editing to generate a model of NFKB1-/- human macrophages. Transcriptomic analysis reveals that activated NFKB1-/- macrophages are more pro-inflammatory than wild type controls and express elevated levels of TNF, IL6, and IL1B, but also have reduced expression of co-stimulatory factors important for the activation of T cells and adaptive immune responses such as CD70, CD83 and CD209. NFKB1-/- THP1 macrophages recapitulate key observations in individuals with NFKB1 haploinsufficiency including decreased IL10 expression. These data supporting their utility as an in vitro model for understanding the role of NFKB1 in human monocytes and macrophages and indicate that of loss of function NFKB1 mutations in these cells is an important component in the associated pathology.

Early-life immune expression profiles predict later life health and fitness in a wild rodent

Individuals differ in the nature of the immune responses they produce, affecting disease susceptibility and ultimately health and fitness. These differences have been hypothesised to have an origin in events experienced early in life that then affect trajectories of immune development and responsiveness. Here we investigate early life influences on immune expression profiles using a natural population of field voles, Microtus agrestis, in which we are able to monitor variation between and within individuals though time by repeat (longitudinal) sampling of individually marked animals. We analysed the co-expression of 20 immune genes in early life to create a correlational network consisting of three main clusters, one of which (containing Gata3, Il10 and Il17) was associated with later life reproductive success and susceptibility to chronic bacterial (Bartonella) infection. More detailed analyses supported associations between early life expression of Il17 and reproductive success later in life, and of increased Il10 expression early in life and later infection with Bartonella. We also found significant association between an Il17 genotype and the early life expression of Il10. Our results demonstrate that immune expression profiles can be manifested during early life with effects that persist through adulthood and that shape the variability among individuals in susceptibility to infection and fitness widely seen in natural populations.

New opportunities for the allergy prevention in brest fed and formula fed infants

В течение последних лет частота встречаемости пищевой аллергии у детей постоянно увеличивается. Одной из наиболее частых причин пищевой аллергии у детей грудного возраста является аллергия на коровье молоко. Распространенность пищевой аллергии коррелирует с растущим объемом исследований и публикаций, изучающих связь факторов окружающей среды с формированием оральной толерантности в раннем возрасте. Управление этим процессом происходит в критический период развития, который получил название «окно возможностей», и ключевая роль принадлежит микробиоте и ее метаболитам. В течение этого периода влияние окружающей среды может иметь долгосрочное воздействие на состав микробиоты, иммунную регуляцию и восприимчивость к болезням. События во время этого критического окна влияют на долгосрочное здоровье человека. Ранняя колонизация сообществом микробов в рамках определенного критического временного окна имеет решающее значение для правильного развития иммунной системы. Грудное молоко остается золотым стандартом вскармливания, но роль его в профилактике пищевой аллергии на сегодняшний день не доказана. Более детальное изучение иммунологических факторов грудного молока и механизмов диалога между микробиотой и иммунной системой, в частности, действия определенных компонентов (пробиотики, пребиотики и метаболиты), помогает разработке новых стратегий профилактики иммуноопосредованных заболеваний, в т. ч. пищевой аллергии. Пребиотики, пробиотики и метаболиты представляют на сегодняшний день огромный интерес для управления аллергией через ускорение формирования иммунологической толерантности не только для первичной, но и для вторичной профилактики при лечении аллергии к белкам коровьего молока. In recent years, the incidence of food allergies in children has been steadily increasing. One of the most common causes of food allergy in infants is cow's milk allergy. The prevalence of food allergy correlates with a growing body of research and publications investigating the relationship of environmental factors and immune development inthe newborn. The «window of opportunity» is critical period of early immune development, and the key role belongs to the microbiota and its metabolites. During this period, environmental influences can have long-term effects on microbiota composition, immune regulation, and susceptibility to disease. Events during this critical window affect long-term human health. Early colonization by the microbial community within a certain critical time window is critical for the proper development of the immune system. Breast milk remains the gold standard for feeding, but its role in preventing food allergies has yet to be proven. A more detailed study of the immunological factors of breast milk and the mechanisms of microbiome-immune crosstalk, in particular, the action of certain components (probiotics, prebiotics and metabolites), helps to develop new preventive strategies. Prebiotics, probiotics and metabolites are of great interest today for managing allergies by accelerating the formation of immunological tolerance not only for primary, but also for secondary prevention in the treatment of allergy to cow's milk proteins.

Infant Formula Based on Milk Fat Affects Immune Development in Both Normal Birthweight and Fetal Growth Restricted Neonatal Piglets

Infant formulas offer an alternative to breast milk for both normal birth weight (NBW) and immunocompromised intrauterine growth restricted (IUGR) infants. Although the lipid fraction in formulas is often derived from vegetable oils, it is unclear if this alters immunological outcomes relative to milk fats or whether these effects differ between IUGR and NBW infants. We hypothesized that replacing vegetable oil with bovine milk fat in infant formula would improve immune development in IUGR and NBW neonates. Two-day old piglets were selected (NBW, n = 18, IUGR, n = 18) and each group of animals were fed formula based on either vegetable oil (VEG) or bovine milk fat (MILK). Animals were reared until day 23/24 and systemic immune parameters were evaluated. Milk-fat feeding decreased blood neutrophil counts and improved neutrophil function while transiently reducing leucocytes’ expression of genes related to adaptive and innate immunity as well as energy metabolism, following in vitro stimulation by live Staphylococcus epidermidis (whole blood, 2 h). However, there were only a few interactions between milk-fat type and birthweight status. Thus, piglets fed milk-fat-based formula had improved neutrophil maturation and suppressed pro-inflammatory responses, compared to those fed vegetable-oil-based formula.