Biology subjects

Megli, C.

Publications and source records attributed to Megli, C..

3 recordsLinked to original sources

bioRxiv2024

Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and {Delta}NSm infection, while live attenuated RVFV vaccines (LAVs; MP-12, {Delta}NSs, and {Delta}NSs/{Delta}NSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent in the maternal-facing side. Type-I and type-III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface. TeaserVaccine strains of Rift Valley fever virus have reduced infection and replication capacity in mammalian placenta

microbiology↗

bioRxiv2023

Bi-directional communication between monocytes and trophoblasts under hypoxia and hypoxia-reperfusion conditions

IntroductionPregnancy-related disorders such as preeclampsia are associated with syncytiotrophoblast (STB) stress and monocyte dysregulation. It remains unclear whether this stress derives from prolonged placental hypoxia or a hypoxia-reperfusion-type injury. Thus, this study investigated how these two models of STB stress impact trophoblast-monocyte interactions. MethodCobalt chloride chemically induced hypoxia in BeWo b30 cells. A transwell coculture system was used to examine trophoblast-monocyte signaling. qPCR quantified gene expression changes following coculture. Monocyte phagocytosis of E. Coli or adhesion to placental cells was determined via flow cytometry. Monocyte migration to placental signals was quantified using a cell counter. ResultsCobalt chloride induced a hypoxic state in BeWo b30s. Reperfusion restored the expression of indirect hypoxia genes and ER stress genes. Coculturing THP-1 monocytes with normoxic, hypoxic, and hypoxic-reperfused BeWo b30s promoted b30 survival but not wound-healing capacity. Compared to hypoxic-reperfused BeWos, hypoxic cells increased monocyte adhesion and inflammatory gene expression, decreased monocyte phagocytosis, and did not change monocyte migration. Finally, placental signaling in early-onset PE decreased monocyte chemotaxis, but monocyte precondition more strongly influenced migration compared to placental state. DiscussionOverall, hypoxic placental signals most effectively recapitulate monocyte functional behavior observed in preeclampsia. Further research is needed to understand spatial and temporal changes in monocyte-trophoblast interactions and pregnancy outcomes. Monocyte chemotaxis to primary placental signals varied by gestational age, maternal diagnosis, and monocyte condition, implying monocytes could be used as functional biomarkers to predict their behavior at the maternal-fetal interface as well as the onset of disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/558721v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@15dae34org.highwire.dtl.DTLVardef@157dec7org.highwire.dtl.DTLVardef@1e2db81org.highwire.dtl.DTLVardef@b90ab6_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface

Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast and decidua organoids from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that trophoblast and decidua organoids basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN- {lambda}2 from trophoblast organoids, and differentially respond to viral infections through the induction of organoid-specific factors. Lastly, we define the differential susceptibility of trophoblast and decidua organoids to human cytomegalovirus (HCMV) and the transcriptional and immunological responses of these organoids to HCMV infection. Our findings establish matched trophoblast and decidua organoids as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.

immunology↗