Placental macrophage (Hofbauer cell) polarization is independent of maternal allergen-sensitization and presence of chorioamnionitis.

BACKGROUND: Macrophages can polarize in which M1/classically activated and M2/alternatively activated macrophages are considered to be the extremes. M1 macrophages are involved in inflammatory reactions, while M2 macrophages are suggested to be involved in homeostasis, parasite killing, tumor promotion, tissue remodeling and in allergic reactions. We hypothesized that polarization of placental macrophages (Hofbauer cells) is influenced by the allergen-sensitization status of the mother and/or the presence of chorioamnionitis, a placental inflammation. This Hofbauer cell polarization might be associated to the intrauterine environment and influence the risk of allergy development for the child. Therefore we aimed to determine the polarization status of Hofbauer cells in health and disease. METHODS: We determined the expression of CD68, CX3CR1, IL-7R, DC-SIGN/CD209 and CD163 in placentas of sensitized versus non-sensitized mothers (n = 17), and placentas with or without histological chorioamnionitis (n = 10) by means of immunohistochemical analysis and quantitative real-time PCR (qPCR). RESULTS: Protein expression of the M1 markers (CX3CR1, IL-7R and CCR7) could not be detected in any of the analyzed samples while the M2 markers (DC-SIGN, CD163 and mannose receptor/CD206) were readily detected. Significant differences between non-sensitized versus sensitized mothers and uncomplicated versus chorioamnionitis complicated pregnancies were not detected at protein or at mRNA expression level. CONCLUSIONS: These results suggest that Hofbauer cells have an M2 phenotype, and that their polarization is not affected by maternal allergen-sensitization or by presence of chorioamnionitis.

IgE in the human placenta: why there?

Immunoglobulin E (IgE) antibodies are key effector molecules in the allergic inflammatory response and are also involved in the protection against extracellular parasites. Allergic symptoms often develop early in life, and the intrauterine environment has been proposed to play an important role in affecting the risk of later allergy development. The placenta constitutes a selective barrier between the maternal and foetal circulation. Recently, we reported that maternal IgE antibodies are present on foetal macrophages in the villous tissue of the human placenta irrespective of maternal allergy status. This review discusses the presence of IgE antibodies in the human placenta and its possible roles in normal and pathologic pregnancy. It also deals with the relationship between placental IgE and development of allergy during childhood. A better understanding of the role of IgE in placenta could give us clues on how to prevent allergy development in the future generations.

Lifestyle and parental allergen sensitization are reflected in the intrauterine environment at gene expression level.

BACKGROUND: Environmental factors, including the intrauterine environment, can influence the risk of allergy development. In the present study, we investigated whether lifestyle and parental allergen sensitization status are reflected at gene expression level in the intrauterine environment. METHODS: mRNA expression of 17 genes was determined by means of quantitative real-time PCR in term placenta of 36 families participating in the ALADDIN study (Assessment of Lifestyle and Allergic Disease During Infancy). Data were analysed using a linear regression model to estimate the influence of lifestyle and parental allergen sensitization on the relative mRNA expression levels. Immunohistochemistry on placenta biopsies was used to verify protein expression. RESULTS: Significant differences in mRNA expression levels were detected at the foetal side of the placenta, where CD14 was expressed at higher levels in placentas from families living on a farm compared to not living on a farm, and IL-12(p40) was expressed at lower levels when the father was sensitized compared to nonsensitized. At the maternal side of the placenta, higher expression of STAT4 and lower expression of GATA3 were detected in families with sensitized compared to nonsensitized mothers, and IL-12(p40) was lower expressed when the families were living on a farm compared to not living on a farm. Immunohistochemistry performed for STAT4 and GATA3 showed that protein and mRNA levels correlated well. CONCLUSION: Living on a farm and parental allergen sensitization are reflected in the intrauterine environment at the gene expression level.

Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates.

BACKGROUND: It is hypothesized that the in utero environment in allergic mothers can affect the neonatal immune responses. The aim of this study was to analyse the effect of maternal allergic disease on cord blood mononuclear cell (CBMC) phenotype and proliferative responses upon allergen stimulation. METHODS: Peripheral blood mononuclear cells (PBMC) from 12 allergic and 14 nonallergic mothers and CBMC from their children were analysed. In the mothers, we determined cell proliferation, production of IL-4 and expression of FOXP3 in response to allergen stimulation. In the children, we evaluated cell proliferation and FOXP3 expression following allergen stimulation. Furthermore, expression of different homing markers on T cells and regulatory T cells and maturity of the T cells and B cell subsets were evaluated directly ex vivo. RESULTS: The timothy- and birch-allergic mothers responded with increased proliferation and/or IL-4 production towards timothy and birch extract, respectively, when compared to nonallergic mothers. This could not be explained by impairment of FOXP3(+) regulatory T cells in the allergic mothers. CBMC proliferation and FOXP3 expression in response to allergens were not affected by the allergic status of the mother. Also, phenotype of T cells, FOXP3(+) regulatory T cells and B cells was not affected by the allergic status of the mother. CONCLUSION: Our results suggest that maternal allergic disease has no effect on the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied here could, however, still affect later development of allergy.

Evidence for allergen-specific IgE of maternal origin in human placenta.

BACKGROUND: Immunoglobulin E (IgE) has been identified on macrophage-like cells in the villi of human placenta, irrespective of the serum IgE levels or allergy status of the mother. The origin of placental IgE is debated and it is not known if it is spontaneously produced, so-called 'natural IgE', or if it has any specificity for certain allergens. The aim of this study was to investigate if placental IgE originates from mother or child and to analyse its specificity. METHODS: Immunoglobulin E was eluted from placenta by lowering the pH. Total and allergen-specific IgEs were measured in placenta eluate, maternal and cord blood plasma by means of ImmunoCAP (Phadia AB). The levels of natural antibodies were determined with an anti-phosphorylcholine (PC) enzyme-linked immunosorbent assay, as natural IgE has been shown in one previous publication with this assay. RESULTS: Detectable amounts of IgE were eluted from 11/12 full-term placentas. Natural (anti-PC) IgE antibodies were detected in low amounts in maternal plasma but not in the placental eluate or in cord blood plasma. There was a significant correlation between the amount of total IgE eluted from placenta and the levels of total IgE in maternal plasma; however, not between maternal and cord blood plasma. Allergen-specific IgE was only found in placental eluates from mothers with specific IgE towards these allergens. Furthermore, there was a significant correlation between the amount of allergen-specific IgE eluted from placenta and the levels of allergen-specific IgE in maternal plasma. Allergen-specific IgE could not be detected in cord blood. CONCLUSION: These results suggest a maternal origin of placental IgE, which can be allergen-specific.

Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis.

We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells in the placenta in allergic as well as non-allergic women suggests that the IgE is of some importance for a successful pregnancy outcome. Here we have investigated the IgE-pattern in 59 placentas from second and third trimesters from Sweden with different degrees of chorioamnionitis and 27 full term placentas from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non-infected placentas, nor between different degrees of chorioamnionitis. The IgE score in the placenta did not correlate with the levels of IgE in maternal serum or plasma. However, the IgE score was significantly higher in second- compared to third-trimester placentas (P = 0.03). This might reflect a maturation time-point in the fetus and in the intrauterine environment during the second trimester, or it might be associated with the increased number of intrauterine fetal deaths in the second trimester.