Search

Your search keyword '"Hauk, Vanesa"' showing total 175 results
Start Over Author "Hauk, Vanesa"
175 results on '"Hauk, Vanesa"'

2. VPAC1 and VPAC2 receptor deficiencies negatively influence pregnancy outcome through distinct and overlapping modulations of immune, trophoblast and vascular functions.

Author

Calo, Guillermina, Hauk, Vanesa, Vota, Daiana, Van, Christina, Gallino, Lucila, Ramhorst, Rosanna, Waschek, James, Pérez Leirós, Claudia, and Condro, Michael

Subjects
Adverse pregnancy outcome models, Innate response at early pregnancy, Placental homeostasis disruption, VPAC1/VPAC2 knockout mice, Animals, Female, Mice, Pregnancy, Placenta, Pregnancy Outcome, Receptors, Vasoactive Intestinal Peptide, Type II, Trophoblasts, Vasoactive Intestinal Peptide, Receptors, Vasoactive Intestinal Polypeptide, Type I, Gene Deletion, Pregnancy Complications
Abstract

Pregnancy outcome relies on the maintenance of immune and metabolic homeostasis at the maternal fetal interface. Maternal and perinatal morbidity and mortality is associated with impaired placental development. Multiple regulatory effects of the endogenous-produced vasoactive intestinal peptide (VIP) on vascular, metabolic and immune functions at the maternal-fetal interface have been reported. Here we studied the involvement of the two primary high affinity receptors for VIP (VPAC1 and VPAC2) on maternal immune response, placental homeostasis and pregnancy outcome. Targeted disruption of each receptor gene led to altered placental structure, vascular and trophoblast functional markers and shaped the functional profiles of macrophages and neutrophils towards a proinflammatory state. Several changes in pregnant mice were receptor specific: ROS production elicited by VIP on neutrophils was selectively dependent on the presence of VPAC1 whereas apoptosis rate was associated with the VPAC2 deletion. In peritoneal macrophages from pregnant mice, levels of MHC-II, TLR2, and IL-10 were selectively altered in VPAC2 receptor-deficient mice, whereas IL-6 gene expression was reduced only in mice lacking VPAC1 receptors. Additionally, MMP9 mRNA in isolated TGCs was reduced in VPAC2 receptor deleted mice, while the percentage of IL-12 cells in post-phagocytosis macrophage cultures was selectively reduced in VPAC2 receptor deficient mice. The results indicate that manipulation of VPAC1 and VPAC2 receptor affects immune, vascular and metabolic environment at the maternal fetal interface. These mouse models offer new approaches to study pregnancy complications adding new perspectives to the development of VPAC receptor-selective drugs.

Published
2023

7. Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

Author

Allo, Verónica C. Martínez, Hauk, Vanesa, Sarbia, Nicolas, Pinto, Nicolás A., Croci, Diego O., Dalotto-Moreno, Tomás, Morales, Rosa M., Gatto, Sabrina G., Cocco, Montana N. Manselle, Stupirski, Juan C., Deladoey, Ángel, Maronna, Esteban, Marcaida, Priscila, Durigan, Virginia, Secco, Anastasia, Mamani, Marta, Dos Santos, Alicia, Pellet, Antonio Catalán, Leiros, Claudia Pérez, Rabinovich, Gabriel A., and Toscano, Marta A.

Published
2020

8. Monocyte immunometabolic reprogramming in human pregnancy: contribution of trophoblast cells

Author

Merech, Fátima, primary, Gori, Soledad, additional, Calo, Guillermina, additional, Hauk, Vanesa, additional, Paparini, Daniel, additional, Rios, Daiana, additional, Lara, Brenda, additional, Doga, Luciana, additional, D'Eramo, Luciana, additional, Squassi, Aldo, additional, Ramhorst, Rossana, additional, Argüello, Rafael J., additional, Pérez Leirós, Claudia, additional, and Vota, Daiana, additional

Published
2023
Full Text
View/download PDF

9. Porphyromonas gingivalis outer membrane vesicles shape trophoblast cell metabolism impairing functions associated to adverse pregnancy outcome

Author

Lara, Brenda, primary, Loureiro, Iñaki, additional, Gliosca, Laura, additional, Castagnola, Lara, additional, Merech, Fátima, additional, Gallino, Lucila, additional, Calo, Guillermina, additional, Sassot, Matías, additional, Ramhorst, Rosanna, additional, Vota, Daiana, additional, Pérez Leirós, Claudia, additional, and Hauk, Vanesa, additional

Published
2023
Full Text
View/download PDF

10. Extracellular Vesicles of Porphyromonas gingivalis Disrupt Trophoblast Cell Interaction with Vascular and Immune Cells in an In Vitro Model of Early Placentation

Author

Lara, Brenda, primary, Sassot, Matías, additional, Calo, Guillermina, additional, Paparini, Daniel, additional, Gliosca, Laura, additional, Chaufan, Gabriela, additional, Loureiro, Iñaki, additional, Vota, Daiana, additional, Ramhorst, Rosanna, additional, Pérez Leirós, Claudia, additional, and Hauk, Vanesa, additional

Published
2023
Full Text
View/download PDF

12. Monocyte immunometabolic reprogramming in human pregnancy: contribution of trophoblast cells.

Author

Merech, Fátima, Gori, Soledad, Calo, Guillermina, Hauk, Vanesa, Paparini, Daniel, Rios, Daiana, Lara, Brenda, Doga, Luciana, D'Eramo, Luciana, Squassi, Aldo, Ramhorst, Rosanna, Argüello, Rafael J., Leirós, Claudia Pérez, and Vota, Daiana

Subjects
TROPHOBLAST, CELL physiology, PREGNANCY, PREGNANT women, MONOCYTES, HUMAN phenotype
Abstract

Immunometabolism research is uncovering the relationship between metabolic features and immune cell functions in physiological and pathological conditions. Normal pregnancy entails a fine immune and metabolic regulation of the maternal-fetal interaction to assist the energetic demands of the fetus with immune homeostasis maintenance. Here, we determined the immunometabolic status of monocytes of pregnant women compared with nonpregnant controls and its impact on monocyte anti-inflammatory functions such as efferocytosis. Monocytes from pregnant women (16-20 wk) and nonpregnant age-matched controls were studied. Single cell-based metabolic assays using freshly isolated monocytes from both groups were carried out in parallel with functional assays ex vivo to evaluate monocyte efferocytic capacity. On the other hand, various in vitro metabolic assays with human monocytes or monocyte-derived macrophages were designed to explore the effect of trophoblast cells in the profiles observed. We found that pregnancy alters monocyte metabolism and function. An increased glucose dependency and enhanced efferocytosis were detected in monocytes from pregnant women at resting states, compared with nonpregnant controls. Furthermore, monocytes display a reduced glycolytic response when stimulated with lipopolysaccharide (LPS). The metabolic profiling of monocytes at this stage of pregnancy was comparable with the immunometabolic phenotypes of human monocytes treated in vitro with human first trimester trophoblast cell conditioned media. These findings suggest that immunometabolic mechanisms are involved in the functional shaping of monocytes during pregnancy with a contribution of trophoblast cells. Results provide new clues for future hypotheses regarding pregnancies complicated by metabolic disorders. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

16. Gingival crevicular fluid from pregnant women impairs trophoblast cell function and trophoblast‐neutrophil interaction

Author

Hauk, Vanesa, primary, D'Eramo, Luciana, additional, Calo, Guillermina, additional, Merech, Fátima, additional, Doga, Luciana, additional, Lara, Brenda, additional, Gliosca, Laura, additional, Massone, Carla, additional, Molgatini, Susana, additional, Ramhorst, Rosanna, additional, Squassi, Aldo, additional, and Pérez Leirós, Claudia, additional

Published
2022
Full Text
View/download PDF

17. Extracellular vesicles of first trimester trophoblast cell line overexpressing VPAC2 induce anti-inflammatory signals in HB cell and maternal monocytes

Author

Paparini, Daniel E., primary, Grasso, Esteban N., additional, Vota, Daiana, additional, Hauk, Vanesa, additional, Merech, Fátima, additional, Lara, Brenda, additional, Izbizky, Gustavo, additional, Abasolo, Juan Ignacio, additional, Ramhorst, Rosanna, additional, and Leirós, Claudia Pérez, additional

Published
2022
Full Text
View/download PDF

21. Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period

Author

Fernández, Laura, primary, Grasso, Esteban, additional, Soczewski, Elizabeth, additional, Gori, Soledad, additional, Calo, Guillermina, additional, Hauk, Vanesa, additional, Sabbione, Florencia, additional, Gallino, Lucila, additional, Martínez, Gustavo, additional, Irigoyen, Marcela, additional, Bestach, Yesica, additional, Pérez Leirós, Claudia, additional, and Ramhorst, Rosanna, additional

Published
2021
Full Text
View/download PDF

24. Placental extracellular vesicles: their potential as biomarkers of gestational complications

Author

Lara, Brenda Ayelen, Merech, Fátima Isabel, Vota, Daiana Marina, Calo, Guillermina, Soczewski, Elizabeth Victoria, Grasso, Esteban Nicolas, Perez Leiros, Claudia, and Hauk, Vanesa Cintia

Subjects
placenta, patologias gestacionales, purl.org/becyt/ford/3 [https], purl.org/becyt/ford/3.1 [https], vesiculas extracelulares
Abstract

Las vesículas extracelulares son importantes mediadores de la comunicación intercelular. Durante la gestación,diversos tipos celulares placentarios como no placentariossecretan vesículas extracelulares a la circulación. Se ha demostrado que las células trofoblásticas liberan permanentemente a la circulación materna vesículas extracelularescargadas con diversas moléculas que modulan la función delas células trofoblásticas, inmunes y vasculares, entre otras.Las complicaciones gestacionales que afectan la placentación, como la restricción del crecimiento intrauterino(RCIU) y la preeclampsia (PE), son un problema de saludpública mundial, ya que son condiciones que contribuyen,en alto grado, a la morbimortalidad materna y neonatal.Hasta ahora, no se dispone de pruebas clínicas quepermitan anticipar el diagnóstico y/o proveer indicadorespredictivos para identificar a las madres con mayor riesgode desarrollar estas complicaciones. En los últimos años,se ha demostrado el potencial de las vesículas extracelulares y su contenido como potenciales biomarcadoresde distintas patologías, por lo que su aplicación despiertaespecial interés en las complicaciones del embarazo. Extracellular vesicles are significant mediators of cellto-cell communication. During pregnancy, placental and non-placental cell types release extracellular vesicles into circulation. Is has been demonstrated that trophoblast cells are continuously releasing vesicles loaded with factors modulating trophoblast, immune and vascular functions. Gestational complications associated to impaired placentation, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), are a global public health problem since they are major contributors to maternal and neonatal morbidity and mortality. Currently, there are no clinical tests that allow early diagnosis and/or provide predictive markers to identify mothers at higher risk of developing these complications. The potential of extracellular vesicles and their content as biomarkers for different pathologies has been demonstrated. For this reason nowadays their application in gestational complications is of special interest. Fil: Lara, Brenda Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fátima Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Soczewski, Elizabeth Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Published
2020

27. Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy

Author

Paparini, Daniel Esteban, primary, Grasso, Esteban, additional, Fernandez, Laura del Carmen, additional, Merech, Fátima, additional, Weingrill‐Barbano, Rodrigo, additional, Correa‐Silva, Simone, additional, Izbizky, Gustavo, additional, Abasolo, José Ignacio, additional, Hauk, Vanesa, additional, Ramhorst, Rosanna, additional, Bevilaqcua, Estela, additional, and Pérez Leirós, Claudia, additional

Published
2020
Full Text
View/download PDF

29. Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

Author

Martínez Allo, Verónica C., primary, Hauk, Vanesa, additional, Sarbia, Nicolas, additional, Pinto, Nicolás A., additional, Croci, Diego O., additional, Dalotto-Moreno, Tomás, additional, Morales, Rosa M., additional, Gatto, Sabrina G., additional, Manselle Cocco, Montana N., additional, Stupirski, Juan C., additional, Deladoey, Ángel, additional, Maronna, Esteban, additional, Marcaida, Priscila, additional, Durigan, Virginia, additional, Secco, Anastasia, additional, Mamani, Marta, additional, Dos Santos, Alicia, additional, Catalán Pellet, Antonio, additional, Pérez Leiros, Claudia, additional, Rabinovich, Gabriel A., additional, and Toscano, Marta A., additional

Published
2020
Full Text
View/download PDF

30. VIP Promotes Recruitment of Tregs to the Uterine–Placental Interface During the Peri-Implantation Period to Sustain a Tolerogenic Microenvironment

Author

Gallino, Lucila, primary, Hauk, Vanesa, additional, Fernández, Laura, additional, Soczewski, Elizabeth, additional, Gori, Soledad, additional, Grasso, Esteban, additional, Calo, Guillermina, additional, Saraco, Nora, additional, Berensztein, Esperanza, additional, Waschek, James A., additional, Pérez Leirós, Claudia, additional, and Ramhorst, Rosanna, additional

Published
2020
Full Text
View/download PDF

31. Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period.

Author

Fernández, Laura, Grasso, Esteban, Soczewski, Elizabeth, Gori, Soledad, Calo, Guillermina, Hauk, Vanesa, Sabbione, Florencia, Gallino, Lucila, Martínez, Gustavo, Irigoyen, Marcela, Bestach, Yesica, Pérez Leirós, Claudia, and Ramhorst, Rosanna

Subjects
HUMAN embryos, NATURAL selection, REGULATORY T cells, INFLAMMATION, BLASTOCYST
Abstract

Problem: Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. Method of Study: We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl‐cAMP, then treated with human blastocysts‐conditioned media (BCM) classified according to their quality. Results: Decidualized cells treated with BCM from impaired developed blastocysts increased IL‐1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. Conclusion: Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo‐endometrial dialogue. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

32. Control of the inflammatory response during pregnancy: Potential role of VIP as a regulatory peptide

Author

Ramhorst, Rosanna Elizabeth, Calo, Guillermina, Paparini, Daniel Esteban, Vota, Daiana Marina, Hauk, Vanesa Cintia, Gallino, Lucila, Merech, Fátima Isabel, Grasso, Esteban Nicolas, and Perez Leiros, Claudia

Subjects
Medicina Básica, PREGNANCY, CIENCIAS MÉDICAS Y DE LA SALUD, VASOACTIVE INTESTINAL POLYPEPTIDE, TROPHOBLAST CELL LINES, IMMUNE HOMEOSTASIS, Inmunología
Abstract

A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti-inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. Fil: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gallino, Lucila. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fatima. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Published
2019
Full Text
View/download PDF

33. Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua

Author

Alippe, Yael, Wang, Leran, Coskun, Reyan, Muraro, Stéfanie P., Zhao, Fang R., Elam-Noll, Michelle, White, J. Michael, Vota, Daiana M., Hauk, Vanesa C., Gordon, Jeffrey I., Handley, Scott A., and Diamond, Michael S.

Abstract

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1−/− or Mavs−/− placentas was associated with greater infection of the adjacent immunocompetent decidua, and heterozygous Mavs+/− or Ifnar1+/− dams carrying immunodeficient fetuses sustained greater maternal viremia and tissue infection than dams carrying wild-type fetuses. Thus, MAVS-IFN signaling in the fetus restricts ZIKV infection in junctional zone trophoblasts, which modulates dissemination and outcome for both the fetus and the pregnant mother.

Published
2024
Full Text
View/download PDF

34. Zika virus infection of first trimester trophoblast cells affects cell migration, metabolism and immune homeostasis control.

Author

Vota, Daiana, Torti, María, Paparini, Daniel, Giovannoni, Federico, Merech, Fátima, Hauk, Vanesa, Calo, Guillermina, Ramhorst, Rosanna, Garcia, Cybele, and Pérez Leirós, Claudia

Subjects
ZIKA virus infections, TROPHOBLAST, BRAIN-derived neurotrophic factor, CELL migration, MATERNAL-fetal exchange, FETAL growth retardation, VASOACTIVE intestinal peptide
Abstract

Zika virus (ZIKV) re‐emerged after circulating almost undetected for many years and the last spread in 2015 was the major outbreak reported. ZIKV infection was associated with congenital fetal growth anomalies such as microcephaly, brain calcifications, and low birth weight related to fetal growth restriction. In this study, we investigated the effect of ZIKV infection on first trimester trophoblast cell function and metabolism. We also studied the interaction of trophoblast cells with decidual immune populations. Results presented here demonstrate that ZIKV infection triggered a strong antiviral response in first trimester cytotrophoblast‐derived cells, impaired cell migration, increased glucose uptake and GLUT3 expression, and reduced brain derived neurotrophic factor (BDNF) expression. ZIKV infection also conditioned trophoblast cells to favor a tolerogenic response since an increased recruitment of CD14+ monocytes bearing an anti‐inflammatory profile, increased CD4+ T cells and NK CD56Dim and NK CD56Bright populations and an increment in the population CD4+ FOXP3+ IL‐10+ cells was observed. Interestingly, when ZIKV infection of trophoblast cells occurred in the presence of the vasoactive intestinal peptide (VIP) there was lower detection of viral RNA and reduced toll‐like receptor‐3 and viperin messenger RNA expression, along with reduced CD56Dim cells trafficking to trophoblast conditioned media. The effects of ZIKV infection on trophoblast cell function and immune‐trophoblast interaction shown here could contribute to defective placentation and ZIKV persistence at the fetal‐maternal interface. The inhibitory effect of VIP on ZIKV infection of trophoblast cells highlights its potential as a candidate molecule to interfere ZIKV infection during early pregnancy. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

41. Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy.

Author

Paparini, Daniel Esteban, Grasso, Esteban, Fernandez, Laura del Carmen, Merech, Fátima, Weingrill‐Barbano, Rodrigo, Correa‐Silva, Simone, Izbizky, Gustavo, Abasolo, José Ignacio, Hauk, Vanesa, Ramhorst, Rosanna, Bevilaqcua, Estela, and Pérez Leirós, Claudia

Subjects
VASOACTIVE intestinal peptide, MONOCYTES, HEALING, HOMEOSTASIS, WOUND healing
Abstract

Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP). Methods: Peripheral blood monocytes were isolated from pregnant and non‐pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT‐qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE‐labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas. Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP‐conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP‐induced decidual factors. Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

46. Sjögren´s Syndrome: relevance of the VIP/VPAC system to homeostasis maintenane and loss

Author

Hauk, Vanesa Cintia and Pérez Leirós, Claudia

Subjects
CELULAS EPITELIALES DE GLANDULA SUBMAXILAR, REGULATORY MACROPHAGES, GLAND HOMEOSTASIS, FAGOCITOSIS, MACROFAGOS REGULATORIOS, SJÖGREN SYNDROME, GLANDULAR EPITHELIAL CELLS, SINDROME DE SJÖGREN, HOMEOSTASIS GLANDULAR, PEPTIDO INTESTINAL VASOACTIVO, VASOACTIVE INTESTINAL PEPTIDE, PHAGOCYTOSIS
Abstract

El Síndrome de Sjögren (SS) es una enfermedad autoinmune crónica que se caracterizapor una progresiva disfunción secretoria con escasa correlación con el daño tisular enlas glándulas. No hay evidencias claras sobre su patogenia y el tratamiento essintomático con un alivio meramente marginal. Se ha propuesto que previo al ataqueautoinmune hay una pérdida en el equilibrio homeostático de las glándulas conactivación de células acinares que podrían aumentar la susceptibilidad del tejido a unarespuesta autoinmune. Los ratones diabéticos no obesos (NOD) son un modelo muyinteresante para estudiar el SS ya que desarrollan una disfunción secretoria conpérdida de temprana de la homeostasis glandular con una moderada infiltraciónlinfocitaria. Los macrófagos, son células plásticas, que tienen un papel central en elmantenimiento de la homeostasis tisular por su función fagocítica para la remoción deproductos de degradación y células apoptóticas, función que realizan en forma ‘silenciosa’ y rápida evitando una respuesta inflamatoria deletérea. El péptidointestinal vasoactivo (VIP) es un neurotransmisor autonómico pro‐secretorio yvasodilatador, que tiene efecto trófico sobre acinos y, junto a sus receptores VPAC, selocaliza en células inmunes con un marcado efecto anti‐inflamatorio einmunomodulador. Basados en los efectos pro‐secretorios y tróficos del VIP sobre los acinos como de suspropiedades anti‐inflamatorias hipotetizamos que la liberación local de VIP pordiversos tipos celulares podría modular procesos apoptóticos e inflamatorios en lainteracción de células inmunes con células epiteliales contribuyendo al mantenimientode la homeostasis tisular glandular. Asimismo, hipotetizamos que estos mecanismosmodulados por VIP se verían alterados en condiciones de ruptura de la homeostasistisular. En este trabajo en primer lugar se estudio el papel del VIP en el mantenimiento de lahomeostasis glandular en el modelo murino NOD. Se observo que hay una disminuciónen la expresión de VIP en las glándulas salivales de ratones NOD que no se observa enla cepa control. La pérdida en la expresión del VIP endógeno se ve asociada con lapérdida de células acinares. Por otro lado, el ‘clearance’ de acinos apoptóticos pormacrófagos se encuentra desregulado en los macrófagos NOD. Sin embargo durante elproceso fagocítico dichos macrófagos adquieren un perfil alternativo de activación. Finalmente, se analizó la contribución del sistema VIP/VPAC en un modelo in vitro deco‐cultivo de células mononucleares totales o monocitos de pacientes con síndrome de Sjögren y células epiteliales de glándula submaxilar (HSG). En primer lugarcaracterizamos el sistema VIP/VPAC en monocitos y su capacidad fagocítica de células HSG apoptóticas donde observamos que los monocitos de pacientes con SS presentanincrementada la expresión del receptor VPAC2 ausente en los monocitos controles y sucapacidad fagocítica se ve alterada. No solo fagocitan en menor cantidad sino queadquieren un perfil fenotípico inflamatorio que no puede ser modulado por VIP. En losco‐cultivos se estudió el perfil funcional y fenotípico de ambos tipos celulares luego dela interacción. Nuestros resultados indican que la interacción puede modular tanto alas células epiteliales como a los monocitos contribuyendo a la generación de unmicroambiente proinflamatorio, donde el VIP fue capaz de modular parcialmentedicho microambiente. Sjögren’s Syndrome (SS) is a chronic autoimmune disease characterized by a deepsecretory dysfunction that correlates poorly with moderate gland damage. SSpathogenesis is still not clearly elucidated and the treatment is symptomatic. It hasbeen proposed that homeostatic loss and acinar activation in the glands precedes theautoimmune response. Non obese diabetic mice (NOD) are a suitable model to study SS since they develop secretory dysfunction with early gland homeostasis loss and amoderate mononuclear infiltration of submandibular glands. Macrophages are plasticcells with a central role in tissue homeostasis maintenance due to their phagocyticfunction to ‘silently’ and rapidly remove apoptotic cells to prevent an inflammatorydeleterious response. Vasoactive intestinal peptide (VIP) is an autonomicneurotransmitter with secretory and vasodilator effects that exerts trophic effects onacini and, along with its VPAC receptors, localizes in immune cells with a strong anti‐inflammatory and immunomodulatory effect. Based on the pro‐secretory and trophic activities of VIP on acini as well as its anti‐inflammatory effect we hypothesized that the local release of VIP by various cell typescould modulate inflammatory and apoptotic processes at the immune‐epithelial cellinteraction contributing to tissue homeostasis maintenance. We hypothesized thatthese VIP‐modulated mechanisms could be altered in homeostasis loss conditions. In this work we first studied the role of VIP in gland homeostasis maintenance in the NOD model. We observed a reduced expression of VIP in salivary glands of NOD micecompared with control mice. The loss of VIP expression was associated with reducednumber of acini. Moreover, apoptotic cell clearance by NOD macrophages wasdefective but the cells acquired an alternative activation profile after phagocytosis. Finally, the contribution of VIP/VPAC system in an in vitro model of immune‐epithelialinteraction was assessed. We co‐cultured PBMC or monocytes from individual SSpatients or control subjects with epithelial cells from a human salivary gland (HSG line). First, we characterized VIP/VPAC system in monocytes and phagocytosis of HSGapoptotic epitelial cells. An increased expression of VPAC2 and reduced phagocytosisof apoptotic cells was found only in SS monocytes. These monocytes also failed toexpress an anti‐inflammatory response upon phagocytosis of apoptotic cells. Thefunctional and phenotypic profile of both epithelial cell and monocytes uponinteraction was then studied. Our results indicate that the interaction can modulateboth epithelial cells and monocytes contributing to the generation of a pro‐inflammatory microenvironment where VIP could only partially modulate thesesignals. Fil: Hauk, Vanesa Cintia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.

Published
2015

49. Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice.

Author

Hauk, Vanesa, Vota, Daiana, Gallino, Lucila, Calo, Guillermina, Paparini, Daniel, Merech, Fátima, Ochoa, Federico, Zotta, Elsa, Ramhorst, Rosanna, Waschek, James, and Leirós, Claudia Pérez

Abstract

Immune homeostasis maintenance throughout pregnancy is critical for normal fetal development. Trophoblast cells differentiate into an invasive phenotype and contribute to the transformation of maternal arteries and the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate vascular remodeling, and a loss of immunologic homeostasis are associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide synthetized in trophoblasts at the maternal-placental interface. It regulates the function of trophoblast cells and their interaction with decidual leukocytes. By means of a murine model of pregnancy in normal maternal background with VIP-deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical for trophoblast function: VIP gene haploinsufficiency results in lower matrix metalloproteinase 9 expression, and reduced migration and invasion capacities. A reduced number of regulatory T cells at the implantation sites along with a lower expression of proangiogenic and antiinflammatory markers were also observed. Findings detected in the implantation sites at early stages were followed by an abnormal placental structure and lower fetal weight. This effect was overcome by VIP treatment of the early pregnant mice. Our results support the relevance of trophoblast-synthesized VIP as a critical factor in vivo for trophoblast-cell function and immune homeostasis maintenance in mouse pregnancy. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

50. Control of the inflammatory response during pregnancy: potential role of VIP as a regulatory peptide.

Author

Ramhorst, Rosanna, Calo, Guillermina, Paparini, Daniel, Vota, Daiana, Hauk, Vanesa, Gallino, Lucila, Merech, Fatima, Grasso, Esteban, and Leirós, Claudia Pérez

Subjects
INFLAMMATION, PREGNANCY, VASOACTIVE intestinal peptide, CELL communication, MACROPHAGES
Abstract

A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti‐inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results