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ZIKA virus infection in human placental cells
106
Abstracts / Placenta 51 (2017) 98e131
P. Zanotto, G. Palmisano, E. Bevilacqua.
D. Vota, D. Paparini, G. Calo, V. Hauk, F. Merech, R. Ramhorst, C. Perez Leiros.
~o Paulo, Sa ~o Paulo, Brazil Instituto de Ci^ encias Biom edicas, Universidade de Sa Zika virus (ZIKV), the mosquito-borne flavivirus that has currently been associated with severe congenital malformations, has also been considered the focus of an ongoing pandemic and public health emergency. Initially limited to sporadic cases in Africa and Asia, since 2015 this infection has spread throughout Brazil and other regions of the Americas. Infection can cause varying symptoms ranging from a subclinical disease to severe conditions such as microcephaly in neonates born to infected mothers and Guillain-Barre syndrome in adults. In this study, we examine in placental tissues the entry of ZIKV and its contribution to the induction of antiviral responses. We show that trophoblast cells are permissive to the entry of ZIKV isolated from a Brazilian patient during the first 6 hours of infection. After 48 hours, viral particles were rarely found, which favors the idea that trophoblast may not be an ideal site for viral replication. The ZIKV permissiveness of the syncytiotrophoblast was confirmed by immunohistochemistry and RT-qPCR. ZIKV induced the expression of specific proteins but did not change cell death rates, which may be associated with restrictions in viral replication. Our preliminary results herein, increase the knowledge on ZIKV the biology, particularly giving the need to develop strategies to contain viral infection during gestation Funding: Fapesp and CNPq.
http://dx.doi.org/10.1016/j.placenta.2017.01.033
THE EPITHELIAL TURNOVER OF THE TROPHOBLAST CONSTITUTES A LOCAL PLACENTAL INNATE IMMUNE RESPONSE AGAINST TRYPANOSOMA CRUZI ~ oz, N. Galanti, J.D. A. Liempi, Ch. Castillo, I. Carrillo, D. Droguett, L. Mun Maya, U. Kemmerling.
Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN, UBA-CONICET, Buenos Aires, Argentina Deep placentation disorders such as preeclampsia are associated with loss of immune homeostasis. Maternal leukocytes are recruited to the maternal-placental interface from the beginning of pregnancy and both normal placentation and the success of pregnancy strongly depend on an appropriate communication established with trophoblast cells. From an immunological standpoint, normal placentation is associated with the maintenance of immune homeostasis through redundant loops of cell-tocell interaction as well as the local release of mediators to sustain an antiinflammatory microenvironment. Among those factors we have proposed the vasoactive intestinal peptide (VIP) and its high affinity receptors VPAC to have a central role. Objective: To explore the relevance of trophoblast cell VIP at the early maternal-placental interface as well as its impact on trophoblast function and interaction with immune cells. Methods: Trophoblast derived cell lines Swan 71 and HTR8 were transfected with a VIP siRNA to knock down its expression or with an irrelevant siRNA as a control. Blood monocytes or neutrophils from healthy donors were co-cultured with trophoblast cells or their conditioned media and immune and trophoblast cell functional profiles were assessed. Results: VIP deficient trophoblast cells exhibited an impaired migration and failed to promote an M2 macrophage profile, as well as to deactivate neutrophils primed with pro-inflammatory stimuli. Conclusions: Results support that the loss of immune homeostasis at the maternal-placental interface involves an impaired trophoblast migration and invasion associated with a defective activation of VIP/VPAC system that fails to modulate both trophoblast function and trophoblast-immune interaction.
http://dx.doi.org/10.1016/j.placenta.2017.01.035
Instituto de Ciencias Biom edicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile Congenital Chagas disease, caused by Trypanosoma cruzi, is partially responsible for the progressive globalization of Chagas disease despite of its low transmission rate. The probability of congenital transmission depends on complex interactions between the parasite, the maternal and fetus/newborn immune responses and placental factors, being the latter the least studied one. During congenital transmission, the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue to have contact with the parasite. Importantly, the epithelial turnover is considered part of the innate immune system since pathogens, prior to cell invasion, must attach to the surface of cells. The trophoblast turnover involves cellular processes such as proliferation, differentiation and apoptotic cell death, all of which are induced by the parasite. Here, we analyse the current evidence about the trophoblast epithelial turnover as a local placental innate immune response. Funding: ERANET-LAC ELAC2014/HID-0328, ENL027/16, UREDES URC-024/ 16 and FONDECYT 1120230, 1130189 and 1130113. http://dx.doi.org/10.1016/j.placenta.2017.01.034
S7 PLACENTAL DYSFUNCTION AND PREGNANCY OUTCOME. TROPHOBLAST CELLS REGULATE IMMUNE CELL FUNCTIONAL PROFILE THROUGH VIP-MEDIATED PATHWAYS
NEW STRATEGIES TO PREVENT PRETERM BIRTH J. Schander, M.V. Bariani, A.P. Dominguez Rubio, F. Correa, F. Jensen, A.M. Franchi. Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina Preterm delivery (PD) is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labour. Our group developed a murine model of preterm labour, induced by injections of bacterial lipopolysaccharide (LPS) that induces a 100% incidence of PD. In this model we assayed new therapeutic tools to prevent preterm labour and to increase offspring survival. Environmental enrichment (EE) strategy has been found to be beneficial in animal models of several neurodegenerative diseases and reverses some consequences of prenatal stress. In general, EE appears to be associated with an overall improvement in the psychological and physical wellbeing of animals. So we assayed the possibility that the EE could prevent the consequences of inflammation induced by bacterial components on pregnancy and labour. In this sense mice were maintained either under a standard condition or upon an enriched environment. Surprisingly we observed that EE prevented preterm delivery in 35% of cases. We also tested two pharmacological treatments to prevent PD. Melatonin, the main product of the pineal gland, contributes to gestation maintenance by stimulating progesterone production and maintaining uterine quiescence. We observed that maternal administration of melatonin prevented LPS-induced PD in 50% of the cases and increased
Abstracts / Placenta 51 (2017) 98e131
P. Zanotto, G. Palmisano, E. Bevilacqua.
D. Vota, D. Paparini, G. Calo, V. Hauk, F. Merech, R. Ramhorst, C. Perez Leiros.
~o Paulo, Sa ~o Paulo, Brazil Instituto de Ci^ encias Biom edicas, Universidade de Sa Zika virus (ZIKV), the mosquito-borne flavivirus that has currently been associated with severe congenital malformations, has also been considered the focus of an ongoing pandemic and public health emergency. Initially limited to sporadic cases in Africa and Asia, since 2015 this infection has spread throughout Brazil and other regions of the Americas. Infection can cause varying symptoms ranging from a subclinical disease to severe conditions such as microcephaly in neonates born to infected mothers and Guillain-Barre syndrome in adults. In this study, we examine in placental tissues the entry of ZIKV and its contribution to the induction of antiviral responses. We show that trophoblast cells are permissive to the entry of ZIKV isolated from a Brazilian patient during the first 6 hours of infection. After 48 hours, viral particles were rarely found, which favors the idea that trophoblast may not be an ideal site for viral replication. The ZIKV permissiveness of the syncytiotrophoblast was confirmed by immunohistochemistry and RT-qPCR. ZIKV induced the expression of specific proteins but did not change cell death rates, which may be associated with restrictions in viral replication. Our preliminary results herein, increase the knowledge on ZIKV the biology, particularly giving the need to develop strategies to contain viral infection during gestation Funding: Fapesp and CNPq.
http://dx.doi.org/10.1016/j.placenta.2017.01.033
THE EPITHELIAL TURNOVER OF THE TROPHOBLAST CONSTITUTES A LOCAL PLACENTAL INNATE IMMUNE RESPONSE AGAINST TRYPANOSOMA CRUZI ~ oz, N. Galanti, J.D. A. Liempi, Ch. Castillo, I. Carrillo, D. Droguett, L. Mun Maya, U. Kemmerling.
Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN, UBA-CONICET, Buenos Aires, Argentina Deep placentation disorders such as preeclampsia are associated with loss of immune homeostasis. Maternal leukocytes are recruited to the maternal-placental interface from the beginning of pregnancy and both normal placentation and the success of pregnancy strongly depend on an appropriate communication established with trophoblast cells. From an immunological standpoint, normal placentation is associated with the maintenance of immune homeostasis through redundant loops of cell-tocell interaction as well as the local release of mediators to sustain an antiinflammatory microenvironment. Among those factors we have proposed the vasoactive intestinal peptide (VIP) and its high affinity receptors VPAC to have a central role. Objective: To explore the relevance of trophoblast cell VIP at the early maternal-placental interface as well as its impact on trophoblast function and interaction with immune cells. Methods: Trophoblast derived cell lines Swan 71 and HTR8 were transfected with a VIP siRNA to knock down its expression or with an irrelevant siRNA as a control. Blood monocytes or neutrophils from healthy donors were co-cultured with trophoblast cells or their conditioned media and immune and trophoblast cell functional profiles were assessed. Results: VIP deficient trophoblast cells exhibited an impaired migration and failed to promote an M2 macrophage profile, as well as to deactivate neutrophils primed with pro-inflammatory stimuli. Conclusions: Results support that the loss of immune homeostasis at the maternal-placental interface involves an impaired trophoblast migration and invasion associated with a defective activation of VIP/VPAC system that fails to modulate both trophoblast function and trophoblast-immune interaction.
http://dx.doi.org/10.1016/j.placenta.2017.01.035
Instituto de Ciencias Biom edicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile Congenital Chagas disease, caused by Trypanosoma cruzi, is partially responsible for the progressive globalization of Chagas disease despite of its low transmission rate. The probability of congenital transmission depends on complex interactions between the parasite, the maternal and fetus/newborn immune responses and placental factors, being the latter the least studied one. During congenital transmission, the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue to have contact with the parasite. Importantly, the epithelial turnover is considered part of the innate immune system since pathogens, prior to cell invasion, must attach to the surface of cells. The trophoblast turnover involves cellular processes such as proliferation, differentiation and apoptotic cell death, all of which are induced by the parasite. Here, we analyse the current evidence about the trophoblast epithelial turnover as a local placental innate immune response. Funding: ERANET-LAC ELAC2014/HID-0328, ENL027/16, UREDES URC-024/ 16 and FONDECYT 1120230, 1130189 and 1130113. http://dx.doi.org/10.1016/j.placenta.2017.01.034
S7 PLACENTAL DYSFUNCTION AND PREGNANCY OUTCOME. TROPHOBLAST CELLS REGULATE IMMUNE CELL FUNCTIONAL PROFILE THROUGH VIP-MEDIATED PATHWAYS
NEW STRATEGIES TO PREVENT PRETERM BIRTH J. Schander, M.V. Bariani, A.P. Dominguez Rubio, F. Correa, F. Jensen, A.M. Franchi. Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Argentina Preterm delivery (PD) is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labour. Our group developed a murine model of preterm labour, induced by injections of bacterial lipopolysaccharide (LPS) that induces a 100% incidence of PD. In this model we assayed new therapeutic tools to prevent preterm labour and to increase offspring survival. Environmental enrichment (EE) strategy has been found to be beneficial in animal models of several neurodegenerative diseases and reverses some consequences of prenatal stress. In general, EE appears to be associated with an overall improvement in the psychological and physical wellbeing of animals. So we assayed the possibility that the EE could prevent the consequences of inflammation induced by bacterial components on pregnancy and labour. In this sense mice were maintained either under a standard condition or upon an enriched environment. Surprisingly we observed that EE prevented preterm delivery in 35% of cases. We also tested two pharmacological treatments to prevent PD. Melatonin, the main product of the pineal gland, contributes to gestation maintenance by stimulating progesterone production and maintaining uterine quiescence. We observed that maternal administration of melatonin prevented LPS-induced PD in 50% of the cases and increased