scholarly journals Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Dhruvesh Patel ◽  
Marnie Newell ◽  
Susan Goruk ◽  
Caroline Richard ◽  
Catherine J. Field

Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results: ARA + DHA maternal diet resulted in higher (p < 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.

2016 ◽  
Vol 41 (5) ◽  
pp. 461-475 ◽  
Author(s):  
Caroline Richard ◽  
Erin D. Lewis ◽  
Catherine J. Field

Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.


2011 ◽  
Vol 2 (1) ◽  
pp. 35-45 ◽  
Author(s):  
S. Gebert ◽  
E. Davis ◽  
T. Rehberger ◽  
C. Maxwell

Early colonisation in the gastrointestinal tract by commensal microbes influences the progressive development and maturity of digestive and immune system functionality in the neonate. Application of strategically selected direct-fed microbials to neonatal pigs may provide an opportunity to dictate a portion of the intestinal microbial community and exert a beneficial influence on these developmental processes. Experiments were conducted to determine the effects of early administration of Lactobacillus brevis strain 1E1 to neonatal piglets (n=224) via a milk supplement system on gastrointestinal microbial counts, villous architecture, and immune cell phenotypes during the lactation phase and after weaning. Pigs administered the direct-fed microbial had lower Escherichia coli counts in the jejunum and ileum (P<0.05), and lower coliform counts in the jejunum compared to unsupplemented pigs (P<0.05). The villous height:crypt depth ratio was greater in the ileum at 9 days of age when pigs were provided L. brevis 1E1 compared to unsupplemented pigs (P<0.05), as well as in the duodenum of pigs supplemented with L. brevis 1E1 at 22 days of age (P<0.05). The number of leukocytes expressing CD2 (P<0.05), CD4 (P=0.07) and MHC-II (P=0.07) was lower in the jejunum of pigs administered L. brevis 1E1 compared to unsupplemented pigs, however direct-fed microbial treatment had no effect on the number of leukocytes expressing CD8, CD25 or SWC3. These data demonstrate that early colonisation of the porcine gastrointestinal tract with L. brevis strain 1E1 during the lactation phase influences the progression of intestinal structure, immune system development, and pathogen establishment, indicating a relationship between early microbial colonisation and development of intestinal maturity and integrity.


2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Francisco J. Pérez-Cano ◽  
Àngels Franch ◽  
Cristina Castellote ◽  
Margarida Castell

Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model.


2020 ◽  
Vol 12 (529) ◽  
pp. eaaw9522 ◽  
Author(s):  
Danika L. Hill ◽  
Edward J. Carr ◽  
Tobias Rutishauser ◽  
Gemma Moncunill ◽  
Joseph J. Campo ◽  
...  

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age, infection, nutrition, and genetics influence immune ontogeny and function is key to informing vaccine design for this at-risk population. We sought to identify factors that shape immune development in children under 5 years of age from Tanzania and Mozambique by detailed immunophenotyping of longitudinal blood samples collected during the RTS,S malaria vaccine phase 3 trial. In these cohorts, the composition of the immune system is dynamically transformed during the first years of life, and this was further influenced by geographical location, with some immune cell types showing an altered rate of development in Tanzanian children compared to Dutch children enrolled in the Generation R population–based cohort study. High-titer antibody responses to the RTS,S/AS01E vaccine were associated with an activated immune profile at the time of vaccination, including an increased frequency of antibody-secreting plasmablasts and follicular helper T cells. Anemic children had lower frequencies of recent thymic emigrant T cells, isotype-switched memory B cells, and plasmablasts; modulating iron bioavailability in vitro could recapitulate the B cell defects observed in anemic children. Our findings demonstrate that the composition of the immune system in children varies according to age, geographical location, and anemia status.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1374
Author(s):  
Jahnavi Aluri ◽  
Megan A. Cooper ◽  
Laura G. Schuettpelz

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in TLR signaling that lead to inborn errors of immunity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Linda Quatrini ◽  
Biancamaria Ricci ◽  
Cecilia Ciancaglini ◽  
Nicola Tumino ◽  
Lorenzo Moretta

Through the release of hormones, the neuro-endocrine system regulates the immune system function promoting adaptation of the organism to the external environment and to intrinsic physiological changes. Glucocorticoids (GCs) and sex hormones not only regulate immune responses, but also control the hematopoietic stem cell (HSC) differentiation and subsequent maturation of immune cell subsets. During the development of an organism, this regulation has long-term consequences. Indeed, the effects of GC exposure during the perinatal period become evident in the adulthood. Analogously, in the context of HSC transplantation (HSCT), the immune system development starts de novo from the donor HSCs. In this review, we summarize the effects of GCs and sex hormones on the regulation of HSC, as well as of adaptive and innate immune cells. Moreover, we discuss the short and long-term implications on hematopoiesis of sex steroid ablation and synthetic GC administration upon HSCT.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2670
Author(s):  
Aysegül Aksan ◽  
Izzet Erdal ◽  
Siddika Songül Yalcin ◽  
Jürgen Stein ◽  
Gülhan Samur

Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = −0.284, p = < 0.001; r = −0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = −0.450, p = < 0.001; r = −0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0–3 months and breast milk OPN levels (r = −0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.


2017 ◽  
Vol 312 (6) ◽  
pp. F971-F981 ◽  
Author(s):  
Fan Fan ◽  
Mallikarjuna R. Pabbidi ◽  
Ying Ge ◽  
Longyang Li ◽  
Shaoxun Wang ◽  
...  

We have reported that the myogenic response of the renal afferent arteriole (Af-art) and middle cerebral artery (MCA) and autoregulation of renal and cerebral blood flow are impaired in Fawn-Hooded Hypertensive (FHH) rats. Transfer of a region of chromosome 1 containing γ-adducin (Add3) from the Brown Norway rat rescued the vascular dysfunction and the development of renal disease. To examine whether Add3 is a viable candidate gene altering renal and cerebral hemodynamics in FHH rats, we knocked down the expression of Add3 in rat Af-arts and MCAs cultured for 36-h using a 27-mer Dicer-substrate short interfering RNA (DsiRNA). Control Af-arts constricted by 10 ± 1% in response to an elevation in pressure from 60 to 120 mmHg but dilated by 4 ± 3% when treated with Add3 DsiRNA. Add3 DsiRNA had no effect on the vasoconstrictor response of the Af-art to norepinephrine (10−7 M). Add3 DsiRNA had a similar effect on the attenuation of the myogenic response in the MCA. Peak potassium currents were threefold higher in smooth muscle cells isolated from Af-arts or MCAs transfected with Add3 DsiRNA than in nontransfected cells isolated from the same vessels. This is the first study demonstrating that Add3 plays a role in the regulation of potassium channel function and vascular reactivity. It supports the hypothesis that sequence variants in Add3, which we previously identified in FHH rats, may play a causal role in the impaired myogenic response and autoregulation in the renal and cerebral circulation.


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