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.

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.

Dual-substrate utilization by Bordetella pertussis.

To improve the cultivation of Bordetella pertussis and take advantage of the newest techniques in monitoring and control, a quantitative description of substrate utilisation is necessary. Growth of the organism is limited by two main substrates. However neither interactive nor non-interactive modelling seem appropriate. A model that combines essential and enhanced kinetics was developed based on experimental observation. Instead of fitting all model parameters at once, a step-wise experimentation procedure was used. Finally two cultivations showed the accuracy of the model.