Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta.

Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes.

Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal Outcomes.

During pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV infection causes a number of disorders, including maculopapular rash, conjunctivitis, and arthralgia. In this paper, we contextualize the immunological aspects involved in the maternal-fetal interface and vulnerability to ZIKV infection, especially the alterations resulting in perinatal outcomes. This highlights the need to develop protective maternal vaccine strategies or interventions that are capable of preventing fetal or even neonatal infection.

Phenotypic characterization of immune cells in fetal tissues of cattle immunized and challenged with Neospora caninum.

The purpose of this work was to characterize the cellular phenotype in inflammatory infiltrates of fetal tissues from pregnant heifers immunized and experimentally challenged with Neospora caninum. Fetuses from 20 heifers separated into 5 groups were obtained. The experiment was designed as follow: Group A, heifers inoculated intravenously with live tachyzoites of Argentine strain NC-6 (n = 4); Group B heifers inoculated subcutaneously with soluble native antigen from the same strain formulated with immune stimulant complexes (ISCOMs) (n = 4); Group C heifers inoculated with recombinant proteins, rNcSAG1, rNcHSP20, rNcGRA7 formulated with ISCOMs (n = 4), Group D heifers inoculated subcutaneously with sterile phosphate buffered solution (n = 4) and Group E heifers inoculated subcutaneously with antigen-free ISCOMs (n = 4). Experimental challenge was performed at 70 days of gestation and all heifers were euthanized 34 days later. Fetal tissues were taken for histological studies. Inflammatory lesions were observed in brain and lung, and immunhistochemistry was used to identify CD3+, CD20+ and MHC II+ cells. The majority of the cells that infiltrate and circumscribe the lesions in the brain and lung tissue expressed MHC II antigen; varying between 70-90% of the total cellular infiltrate. CD3+ cells were also present within the lesions, contributing to up to 30% of the inflammatory cells. CD20+ cells appeared as a marginal group, in some cases, with a range between 10 and 25%. As expected, the immunolabeling of MHC II + and CD3 + cells in fetal tissues was associated with fetal infection with N. caninum. There were statistically significant differences in the distribution and population of the inflammatory infiltrate in relation to the immunogenic treatment and the type of tissue, with inflammatory cells being markedly less extensive fetuses from group A (dams previously exposed to N. caninum) and in brain tissue. This work showed that Neospora-infection induced MHC II+ and CD3+ cells in bovine fetuses from dams receiving experimental vaccines.

O feto é um ser alogênico de sucesso / The fetus is a successful allogeneic being

O feto é um ser alogênico de sucesso. O feto é um aloenxerto natural bem tolerado pelo organismo materno. Vários fatores contribuem para a tolerância materna ao feto: 1. O útero é um local do corpo imunologicamente privilegiado, protegido por uma barreira tecidual não imunogênica; 2. A promoção de uma resposta imunossupressora local pela mãe: a. A molécula HLA-G do MHC de classe Ib, expressa nas células da placenta, impede que as células NK matem a placenta; b. A catabolização do aminoácido essencial triptofano pela placenta impede que as células T da mãe tenham acesso ao feto; c. A secreção das citocinas TGF-ß, IL-4 e IL-10, pelo epitélio uterino e trofoblasto, tende a suprimir as respostas das células T da mãe; d. A secreção das citocinas TGF-ß e IL-10, pelas células T reguladoras, também inibe as respostas de células T maternas.(AU)

The fetus is a successful allogeneic being. The fetus is a natural allograft well tolerated by the maternal organism. Several factors contribute to maternal fetal tolerance: 1. The uterus is an immunologically privileged body site, protected by a non-immunogenic tissue barrier. 2. Promoting a local immunosuppressive response by the mother: a. The MHC class Ib HLA-G molecule, expressed on placental cells, prevents NK cells from killing the placenta; b. The catabolization of the essential amino acid tryptophan by the placenta prevents the mother's T cells from accessing the fetus; c. Secretion of TGF-ß, IL-4 and IL-10 cytokines by the uterine and trophoblast epithelium tends to suppress the T-cell responses of the mother; d. Secretion of TGF-ß and IL-10 cytokines by regulatory T cells also inhibits maternal T cell responses.(AU)

Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model.

While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control-rats received saline; Adjuvant-rats received the adjuvant MPLA, and Vaccine-rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy.

Genotyping approach for non-invasive foetal RHD detection in an admixed population.

BACKGROUND: Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. Considering that the Argentine genetic background is the result of generations of intermixing between several ethnic groups, we evaluated the diagnostic performance of a non-invasive foetal RHD determination strategy to guide targeted antenatal RhD immunoprophylaxis. This algorithm is based on the analysis of four regions of the RHD gene in cell-free foetal DNA in maternal plasma and maternal and paternal RHD genotyping. MATERIALS AND METHODS: DNA from 298 serologically D negative pregnant women between 19-28 weeks gestation were RHD genotyped. Foetal RHD status was determined by real-time PCR in 296 maternal plasma samples. In particular cases, RHDΨ and RHD-CE-Ds alleles were investigated in paternal DNA. Umbilical cord blood was collected at birth, and serological and molecular studies were performed. RESULTS: Of the 298 maternal samples, 288 were D-/RHD- and 10 D-/RHD+ (2 RHD*DAR; 5 RHD-CE-Ds; 3 RHDΨ). Plasma from RHD*DAR carriers was not analysed. Real-time PCR showed 210 RHD+ and 78 RHD- foetuses and 8 inconclusive results. In this latter group, paternal molecular studies were useful to report a RHD negative status in 5 foetuses while only 3 remained inconclusive. All the results, except one false positive due to a silent allele (RHD[581insG]), agreed with the neonatal typing performed in cord blood. DISCUSSION: The protocol used for non-invasive prenatal RHD genotyping proved to be suitable to determine foetal RHD status in our admixed population. The knowledge of the genetic background of the population under study and maternal and paternal molecular analysis can reduce the number of inconclusive results when investigating foetal RHD status.

Characterization of Natural Killer Cells and Cytokines in Maternal Placenta and Fetus of Diabetic Mothers.

The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16(+)CD56(-) NK cells increased, whereas that of CD16(+)CD56(+) decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16(+)CD56(-) and CD16(-)CD56(+). The placental extravillous layer of GDM and DM-2 showed an increase of CD16(+)CD56(-) cells and, irrespective of region, the proportion of CD16(-)CD56(+) cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1ß and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16(+).

In utero exposure to pets is associated with asthma and wheezing in Mexican American children.

OBJECTIVE: To examine the associations of in utero and early life exposure to cats/dogs and birds with the risk of lifetime doctor-diagnosed asthma and other respiratory conditions in a sample of Mexican American (MA) children 4-18 years of age. METHODS: This study is a population-based cross-sectional investigation of 1816 MA children. We conducted multiple logistic models examining the relationship of asthma and wheezing with exposures to cats/dogs and birds in utero, infancy and at the time of the survey adjusted for country of birth, family history of asthma/allergies, antibiotics use in infancy and other covariates. RESULTS: In adjusted analyses, in utero exposure to cats/dogs and birds jointly was associated with increased odds of asthma (adjusted odds ratio (aOR): 2.89; 95% confidence interval (CI): 1.34-6.23), ever wheezing (aOR: 1.96; 95% CI: 1.11-3.46) and current exercise-induced wheezing (aOR: 3.16; 95% CI: 1.27-7.85) compared to children not exposed to these pets in utero. Children who were exposed to both cats/dogs and birds in utero had an elevated, albeit statistically non-significant, odds of current wheezing. Exposures in infancy and at the time of the survey to cats/dogs and birds were not associated with asthma or wheezing. CONCLUSIONS: In utero exposure to pets might be associated with an increased risk of asthma and respiratory conditions in a sample of non-affluent MA children.

Índice de massa corporal, circunferência da cintura e hipertensão arterial em estudantes / Índice de masa corporal, circunferencia de la cintura y hipertensión arterial en estudiantes / Body mass index, waist circumference, and arterial hypertension in students

RESUMO Objetivo: investigar qual o melhor preditor antropométrico de hipertensão arterial em alunos de escolas privadas. Método: estudo transversal, com amostra composta por 286 alunos com idade de 10 a 14 anos de duas escolas privadas de Paranavaí-Paraná. As variáveis analisadas foram: índice de massa corporal, circunferência de cintura e pressão arterial. Na análise estatística foram utilizados os testes de correlação parcial de Pearson e a regressão logística multivariada, considerando-se p<0,05. Resultados: os dois indicadores antropométricos demonstraram fracas correlações com os níveis sistólicos e diastólicos, com coeficientes (r) variando de 0,27 à 0,36 (p< 0,001). Na análise multivariada, o único indicador antropométrico associado ao risco de hipertensão arterial foi a circunferência de cintura (OR= 2,3; IC 95%: 1,1-4,5) independente da idade e gênero. Conclusão: nesta faixa etária, a circunferência de cintura parece ser melhor do que índice de massa corporal como preditor de hipertensão arterial. .

RESUMEN Objetivo: investigar cuál es el mejor predictor antropométrico de la hipertensión arterial en los alumnos de escuelas particulares. Métodos: estudio transversal con muestra compuestas por 286 alumnos con edad de 10 a 14 años de dos escuelas privadas de Paranavaí-Paraná. Las variables analizadas fueron: índice de masa corporal, circunferencia de la cintura y la presión arterial sistólica y diastólica. En el análisis de estadísticas fueron utilizadas las pruebas de correlación parcial de pearson y regresión logística multivariada considerándose p<0.05. Resultados: los dos indicadores antropométricos han mostrado débiles correlaciones con los niveles sistólicos y diastólicos, con Coeficientes (r) variando de 0,27 a 0,36 (p<0,001). En el análisis multivariado el único indicador antropométrico asociado al riesgo de hipertensión arterial fue la circunferencia de la cintura (OR=2,3; IC 95%: 1,1- 4,5) independiente de la edad y el género. Conclusión: en este grupo de edad, la circunferencia de la cintura parece ser mejor de que el índice de masa corporal como predictor de la hipertensión arterial. .

ABSTRACT Objective: to investigate what is the best anthropometric predictor of arterial hypertension among private school students. Method: this was a cross-sectional study with 286 students between the ages of 10 and 14 from two private schools in the city of Paranavaí, Paraná, Brazil. The following variables were analyzed: body mass index, waist circumference and blood pressure. Statistical analysis was conducted with Pearson’s partial correlation test and multivariate logistic regression, with p<0.05. Results: both anthropometric indicators displayed weak correlation with systolic and diastolic levels, with coeffi cients (r) ranging from 0.27 to 0.36 (p < 0.001). Multivariate analysis showed that the only anthropometric indicator associated with arterial hypertension was waist circumference (OR= 2.3; 95% CI: 1.1-4.5), regardless of age or gender. Conclusion: this age group, waist circumference appeared to be a better predictor for arterial hypertension than body mass index. .

Inmunología perinatal / Perinatal immunology

Se ha considerado que el útero gestante es un lugar inmunológicamente privilegiado, donde el feto es protegido del rechazo por el sistema inmune materno, mediante un amplio repertorio de estrategias de evasión que contribuye a la sobrevivencia del feto. La gestación en sí misma constituye un acontecimiento de equilibrio inmunológico y la tolerancia inmunológica permite la progresión del embarazo, donde participan una secuencia sincronizada de eventos que se inicia desde la concepción y fertilización para dar lugar a la implantación y progresa hasta alcanzar un embarazo a término. El sistema inmune es la principal barrera que poseemos para protegernos de las infecciones. Durante la vida intrauterina, el feto está protegido por la madre de las agresiones externas, por lo que no necesita que su sistema inmunológico sea operativo, sin embargo, al nacer, recibe una avalancha de elementos extraños, por lo que necesitará disponer de cierta protección, así como una preparación para ejecutar las defensas necesarias para su protección inmunológica. La inmunidad sérica durante la vida fetal queda limitada a la transferencia a través de la placenta de IgG materna, a pesar de que el feto tiene la facultad de sintetizar inmunoglobulinas desde las primeras etapas de la gestación. Al nacimiento, el niño tiene su sistema inmunológico completo, aunque inmaduro, pero es capaz de responder a los estímulos antigénicos. Tiene múltiples anormalidades en el desarrollo de su sistema inmune, que involucran a los anticuerpos/inmunoglobulinas, complemento y granulocitos pudiendo contribuir a la alta incidencia de sus infecciones. El recién nacido carece de memoria inmunológica debido a que, en condiciones normales, el feto está exento de estímulos producidos por antígenos extraños. Dicha memoria se va adquiriendo a medida que entra en contacto con los diferentes antígenos. Se obtendrá cierta protección a las infecciones entéricas gracias a las IgA que aporta la lactancia materna. La exposición prenatal y postnatal a productos microbianos ambientales que pueden activar la inmunidad innata, puede acelerar el proceso de maduración del sistema inmune.(AU)

It has been considered the pregnant women`s womb as an immunological exceptional place, where fetus is protected against been rejected because of maternal immune system by means of a wide groups of evasive strategies that help in its survival. Pregnancy itself is an immunological equilibrium state and the immunological tolerance allow the progression of this event, where participate a synchronized sequence of biological events started from conception and fertilization to allow the implantation, and progress until to reach the pregnancy end. The immune system is our main barrier against infections. During intrauterine life fetus is protected by the mother against external aggressions, therefore he don`t need an operative immune system, nevertheless, at birth the new organisms receive an avalanche of strange elements needing some kind of protection as well as a preparation to carry out the necessary defense for his immunological protection. Serum immunity during fetal life is limited to the transference of maternal IgG through placenta, despite fetus capability to synthesize immunoglobulins from first stages of gestation. At birth the babe has a complete immunological system although immature but capable to respond to antigenic stimulus. He has multiples abnormalities in the immune system development that take account antibodies/immunoglobulin, complement and granulocytes contributing to his high incidence of infections. Newborn lack immunological memory because in normal conditions fetus is not stimulated by odd antigens. This memory is acquired through the contact with different antigens. It will be obtained some protection against enteric infections because IgA from maternal lactation. The prenatal and postnatal exposition to environmental microbial products that activate the innate immunity can accelerate the immune system maturing process.(AU)

The role of pregnancy-specific glycoprotein 1a (PSG1a) in regulating the innate and adaptive immune response.

Among several explanations for the acceptance of the fetus, the one that suggests that the maternal immune system is suppressed or modified has been the subject of many studies. Thus, it has been proposed that the cells of innate immune system might be able to distinguish the pregnant from the non-pregnant state producing a signal, the so-called signal P. We have previously proposed that pregnancy-specific glycoprotein 1a (PSG1a), a representative member of the main glycoprotein family secreted by placental trophoblast, may modulate the activation of antigen-presenting cells promoting the T-cell shift of the maternal cell immunity toward a less harmful phenotype. In this review, we summarize current knowledge concerning the contribution of pregnancy-specific glycoprotein 1a (PSG1a) to modulate the maternal innate and adaptive immune response in order to assure a successful pregnancy.

Tolerance induction at the early maternal-placental interface through selective cell recruitment and targeting by immune polypeptides.

Pregnancy challenges immune cells and immunomodulatory circuits of the mother and the developing fetus to dynamically adapt to each other in an homeostatic and tolerant environment for fetal growth. This entails the coordination of multiple cellular processes all devoted to accommodate and nourish the fetus while protecting the mother from endogenous and exogenous threatens. From the earliest stages of pregnancy, several strategies to efficiently communicate immune and trophoblast cells within the interface or at a distance were identified and chemokines might act at on different targets through direct or indirect mechanisms. Here, we briefly review some mechanisms of T regulatory cell recruitment to the early maternal-placental interfaces to accomplish immunotolerance and homeostatic control and we discuss evidence on two locally released polypeptides, RANTES (regulated on activation, normal, T-cell expressed, and secreted) and vasoactive intestinal peptide (VIP), as novel contributors to the multiplicity of immune tolerant responses and uterine quiescence requirements.

'Sweetening' pregnancy: galectins at the fetomaternal interface.

Successful mammalian pregnancy relies upon acceptance of a semi-allogeneic fetus by the maternal immune system. Lessons learned from studies on protective immunity to microbial infections and tumours, prevention of autoimmunity, and allograft rejection have contributed to delineate the mechanisms leading to T-cell tolerance at the fetomaternal interface. Recent observations highlight the contribution of galectins, a family of endogenous glycan-binding proteins, to critical biological events occurring during mammalian gestation, including immune cell tolerance, inflammation, implantation, and angiogenesis. These multifunctional lectins can hierarchically control a cascade of immunoregulatory events including the expansion, recruitment, and function of regulatory T cells, the promotion of tolerogenic dendritic cells, and the execution of T-cell death programs. In addition, galectins can control cell adhesion and signaling events critical for implantation and are involved in fundamental processes linking tissue hypoxia to angiogenesis. In an attempt to integrate the regulatory roles of galectins to immunological and vascular programs operating during pregnancy. Here we outline the regulated expression and function of individual members of the galectin family within the fetoplacental unit and their biological implications for the development and preservation of successful pregnancies.

Maternal LAMP/p55gagHIV-1 DNA immunization induces in utero priming and a long-lasting immune response in vaccinated neonates.

Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.

Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters?

INTRODUCTION: Alloimmunization is the main cause of fetal anemia. There are not many consistent analyses associating antenatal parameters to perinatal mortality in transfused fetuses due to maternal alloimmunization. The study aimed to determine the prognostic variables related to perinatal death. MATERIAL AND METHODS: A cohort study analyzed 128 fetuses treated with intrauterine transfusion (IUT), until the early neonatal period. Perinatal mortality was associated with prognostic conditions related to prematurity, severity of fetal anemia and IUT procedure by univariated logistic regression. Multiple logistic regression was used to compute the odds ratio (OR) for adjusting the hemoglobin deficit at the last IUT, gestational age at birth, complications of IUT, antenatal corticosteroid and hydrops. RESULTS: Perinatal mortality rate found in this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI: 1.04-1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38-0.74) and the presence of transfusional complications (OR: 5.43, 95% CI: 142-20.76) were significant in predicting fetal death. CONCLUSION: Perinatal mortality prediction in transfused fetuses is not associated only to severity of anemia, but also to the risks of IUT and prematurity.

[Trypanosoma cruzi infection in pregnant mice induces a cellular immune response with citokines production in their fetuses]. / La infección por Trypanosoma cruzi en ratones gestantes induce una respuesta inmune celular con producción de citocinas en sus fetos.

The objective of this study was to detect the cytokines IFN-gamma, IL-4 and IL-10 expressed by CD4+ T cells in tissues of fetal mice with acute chagasic infection. For this, we examined the fetuses of NMRI mice whose mothers were infected with 22x10(3) metacyclic trypomastigotes of the M/HOM/BRA/53/Y strain of T. cruzi and made pregnant during the acute phase of infection. For the detection and localization of inflammatory infiltrates, nest parasites, antigens of T. cruzi a nd cytokines w eused hematoxylin-eosin techniques, peroxidase-anti-peroxidase and immunofluorescence. The immunohistochemical study revealed the presence of inflammatory infiltrates and antigens with amastigote nests in fetal skeletal muscle. CD4 + T cells producing IFN-gamma, as well as deposits of IFN-gamma and IL-10, were detected in sections of placenta, heart and skeletal muscle of fetuses of mice infected, while CD4+/IL-10+ was found only in skeletal muscle; in addition, deposits of IL-4 were detected only in placentas of healthy mice. These results indicate that fetuses are capable of generating their own immune response to antigens transmitted by their mother, which induces the secretion of cytokines and that, acting in synergy with the maternal antibodies, confer them a state of protection against infection; and that the transmission of the parasite depends on factors specific to each mother, which may modify its ability to control such transmission at the placental or systemic levels.

La infección por Trypanosoma cruzi en ratones gestantes induce una respuesta inmune celular con producción de citocinas en sus fetos / Trypanosoma cruzi infection in pregnant mice induces a cellular immune response with citokines production in their fetuses

El objetivo del presente estudio fue detectar las citocinas IFN-g, IL-4 e IL-10 expresadas por células T CD4+ en tejidos de fetos de ratones con infección chagásica aguda. Para ello, se examinaron fetos de ratones NMRI cuyas madres fueron infectadas con 22×10³ tripomastigotes metacíclicos de la cepa M/HOM/BRA/53/Y de T. cruzi y preñadas durante la fase aguda de la infección. Para la detección y localización de infiltrados inflamatorios, nidos de parásitos, antígenos de T. cruzi y citocinas se emplearon las técnicas de hematoxilina-eosina, peroxidasa-anti-peroxidasa e inmunofluorescencia indirecta. Se detectaron infiltrados inflamatorios y antígenos con nidos de amastigotes en el músculo esquelético fetal. Células T CD4+ productoras de IFN-g así como depósitos de IFN-g e IL-10 fueron detectados en las secciones de placenta, corazón y músculo esquelético de fetos de ratones infectadas, mientras que células CD4+/IL-10+ se encontraron sólo en músculo esquelético, adicionalmente se detectaron depósitos de IL-4 sólo en placentas de ratones sanas. Estos resultados indican que el feto es capaz de generar una respuesta inmune propia frente a antígenos transmitidos por su madre, lo cual induce la secreción de citocinas que actuando en sinergia con los anticuerpos maternos le confieren un estado de protección contra la infección, y que la transmisión del parásito depende de factores específicos de cada madre, la cual puede modificar su capacidad de controlar tal transmisión ya sea a nivel placentario o sistémico.

The objective of this study was to detect the cytokines IFN-g, IL-4 and IL-10 expressed by CD4+ T cells in tissues of fetal mice with acute chagasic infection. For this, we examined the fetuses of NMRI mice whose mothers were infected with 22×10³ metacyclic trypomastigotes of the M/HOM/BRA/53/Y strain of T. cruzi and made pregnant during the acute phase of infection. For the detection and localization of inflammatory infiltrates, nest parasites, antigens of T. cruzi and cytokines we used hematoxylin-eosin techniques, peroxidase-anti-peroxidase and immunofluorescence. The immunohistochemical study revealed the presence of inflammatory infiltrates and antigens with amastigote nests in fetal skeletal muscle. CD4 + T cells producing IFN-g, as well as deposits of IFN-g and IL-10, were detected in sections of placenta, heart and skeletal muscle of fetuses of mice infected, while CD4+/IL-10+ was found only in skeletal muscle; in addition, deposits of IL-4 were detected only in placentas of healthy mice. These results indicate that fetuses are capable of generating their own immune response to antigens transmitted by their mother, which induces the secretion of cytokines and that, acting in synergy with the maternal antibodies, confer them a state of protection against infection; and that the transmission of the parasite depends on factors specific to each mother, which may modify its ability to control such transmission at the placental or systemic levels.

IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research.

A review of immune transfer by the placenta.

Feto-maternal immune transfer occurs via both the placenta in utero and colostrum after birth. The layers between the maternal and fetal circulation systems, known as the placental barrier, regulate immune transfer to the fetus via the placenta. The placental barrier, as well as the type of placental structure, is species specific. The extent of transfer of antibodies from mother to fetus is related to the number of placental barrier layers. Passive immunity via the colostrum is essential in species in which the type of placentation impedes contact between maternal and fetal circulation systems, hindering the transfer of antibodies. In these species, susceptibility to neonatal infections is increased if colostrum is not ingested. Acquired antibodies are of extreme importance for adaptation of the neonate to the extrauterine environment. Based on the aforementioned factors, it was observed that in synepitheliochorial and epitheliochorial placentas immune transfer via the placenta is not possible, except in cases of placental alteration (e.g., placentitis). On the other hand, the mechanism of transfer in endothelial and hemochorial placentas is facilitated compared with other placentas. We conclude that there are no appreciable qualitative differences between the two mechanisms of transfer (placenta and colostrum) and that immune protection in the neonate can be attained by either mechanism.