271 research outputs found

    Childhood Immune Maturation and Allergy Development: Regulation by Maternal Immunity and Microbial Exposure

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    Problem The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation, resulting in an abnormal post-natal immune maturation. Most studies investigating the underlying mechanisms have focused on post-natal microbial exposure. Also, the maternal microbial environment during pregnancy may program the immune development of the child, however. Method of study This review focuses on how maternal immunity and microbial exposures regulate childhood immune and allergy development. Results Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated post-natal environment, but potentially also increasing disease susceptibility in the offspring. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. Conclusion Efficacious preventive measures, required to combat the allergy epidemic, may be identified by determining how the immune interaction between mother and child is influenced by microbial factors.This is the pre-reviewed version of the following article:Maria Jenmalm, Childhood Immune Maturation and Allergy Development: Regulation by Maternal Immunity and Microbial Exposure, 2011, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (66), 75-80.which has been published in final form at: http://dx.doi.org/10.1111/j.1600-0897.2011.01036.xCopyright: Blackwell Publishing Ltdhttp://eu.wiley.com/WileyCDA/Brand/id-35.htm

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    of L. reuteri in saliva. T. Abrahamsson and M. Jenmalm have received honoraria from The aim of this study was to evaluate the effect, on oral health at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730 to the mothers during the last month of gestation and to the children through the first year of life. The stud

    Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life

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    Background: Early colonization with a diverse microbiota seems to play a crucial role for appropriate immune maturation during childhood. Breastmilk microbiota is one important source of microbes for the infant, transferred together with maternal IgA antibodies. We previously observed that allergy development during childhood was associated with aberrant IgA responses to the gut microbiota already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breastfed infants.Objective: To determine the microbial composition and IgA‐coated bacteria in breastmilk in relation to allergy development in children participating in an intervention trial with pre‐ and post‐natal Lactobacillus reuteri supplementation. Methods: A combination of flow cytometric cell sorting and 16S rRNA gene sequencing was used to characterize the bacterial recognition patterns by IgA in breastmilk samples collected one month post‐partum from 40 mothers whose children did or did not develop allergic and asthmatic symptoms during the first 7 years of age. Results: The milk fed to children developing allergic manifestations had significantly lower bacterial richness, when compared to the milk given to children that remained healthy. Probiotic treatment influenced the breastmilk microbiota composition. However, the proportions of IgA‐coated bacteria, the total bacterial load and the patterns of IgA‐coating were similar in breastmilk between mothers of healthy children and those developing allergies. Conclusion: Consumption of breastmilk with a reduced microbial richness in the first month of life may play an important role in allergy development during childhood.This study was supported by the Spanish Ministry of Economy and Competitiveness (Grant No. BIO2015‐68711‐R) to Alex Mira. This study was supported by the Swedish Research Council (2016‐01698), the Swedish Heart and Lung Foundation (20140321 and 20170365) and the Cancer and Allergy Foundation to Maria C. Jenmalm. This study was supported by European Research Council (ERC‐starting grant 639226) to M. Carmen Collado.Peer reviewe

    First‐trimester trophoblasts obtained by chorionic villus sampling maintain tolerogenic and proteomic features in successful pregnancies despite a history of unexplained recurrent pregnancy loss

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    Problem While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. Method of study Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4(+)T cells into immune regulatory phenotypes, as detected by flow cytometry. Results Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. Conclusion Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL.Funding Agencies|Swedish Research CouncilSwedish Research Council [2018-02776]; Linkoping University; Tor Vergata University; ALF Grants</p

    Altered early infant gut microbiota in children developing allergy up to 5 years of age

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    Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture-dependent techniques, studied genera of bacteria and the follow-up period was limited to 2 years. To relate gut microbiota in early infancy, notably bifidobacteria and lactobacilli at species level, to allergy development during the first 5 years of life and study if environmental factors influence the early infant gut microbiota. Fecal samples were collected at 1 week, 1 month and 2 months after birth from 47 Swedish infants, followed prospectively to 5 years of age. Bacterial DNA was analysed with real-time PCR and related to allergy development, family size as well as endotoxin and Fel d 1 levels in house dust samples. Primers binding to C. difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis were used. Children regarded as allergic manifested allergic symptoms and were skin prick test positive during their first 5 years while non-allergic children were neither. Children who developed allergy were significantly less often colonized with lactobacilli group I (Lactobacillus (L.) rhamnosus, L. casei, L. paracasei), Bifidobacterium adolescentis and C. difficile during their first 2 months. Infants colonized with several Bifidobacterium species had been exposed to higher amounts of endotoxin and grew up in larger families than infants harbouring few species. A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allergy, family size and endotoxin exposure.The definitive version is available at www.blackwell-synergy.com:Ylva Sjögren, Maria Jenmalm, Malin Böttcher, Bengt Björkstén and E Sverremar-Ekström, Altered early infant gut microbiota in children developing allergy up to 5 years of age, 2009, CLINICAL AND EXPERIMENTAL ALLERGY, (39), 4, 518-526.http://dx.doi.org/10.1111/j.1365-2222.2008.03156.xCopyright: Blackwell Publishing Ltdhttp://www.blackwellpublishing.com

    Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro

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    Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anticoagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-gamma secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage

    The mother-offspring dyad: microbial transmission, immune interactions and allergy development

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    The increasing prevalence of allergy in affluent countries may be caused by reduced intensity and diversity of microbial stimulation, resulting in abnormal postnatal immune maturation. Most studies investigating the underlying immunomodulatory mechanisms have focused on postnatal microbial exposure, for example demonstrating that the gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, it is also becoming increasingly evident that the maternal microbial environment during pregnancy is important in childhood immune programming, and the first microbial encounters may occur already in utero. During pregnancy, there is a close immunological interaction between the mother and her offspring, which provides important opportunities for the maternal microbial environment to influence the immune development of the child. In support of this theory, combined pre- and postnatal supplementations seem to be crucial for the preventive effect of probiotics on infant eczema. Here, the influence of microbial and immune interactions within the mother-offspring dyad on childhood allergy development will be discussed. In addition, how perinatal transmission of microbes and immunomodulatory factors from mother to offspring may shape appropriate immune maturation during infancy and beyond, potentially via epigenetic mechanisms, will be examined. Deeper understanding of these interactions between the maternal and offspring microbiome and immunity is needed to identify efficacious preventive measures to combat the allergy epidemic.Funding Agencies|Nutricia/Danone</p

    Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy

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    Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (pandlt;0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.Original Publication: Martina Sandberg, Anne Frykman, Yvonne Jonsson, Marie Persson, Jan Ernerudh, Göran Berg, Leif Matthiesen, Christina Ekerfelt and Maria Jenmalm, Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 1, 82-88. http://dx.doi.org/10.1016/j.jri.2009.04.003 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/</p

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