title: Macrophage Exosomes Induce Placental Inflammatory Cytokines: A Novel Mode of Maternal-Placental Messaging.
abstract: During pregnancy, the placenta forms the interface between mother and fetus. Highly controlled regulation of trans-placental trafficking is therefore essential for the healthy development of the growing fetus. Extracellular vesicle-mediated transfer of protein and nucleic acids from the human placenta into the maternal circulation is well documented; the possibility that this trafficking is bi-directional has not yet been explored but could affect placental function and impact on the fetus.We hypothesized that the ability of the placenta to respond to maternal inflammatory signals is mediated by the interaction of maternal immune cell exosomes with placental trophoblast. Utilizing the BeWo cell line and whole placental explants, we demonstrated that the human placenta internalizes macrophage-derived exosomes in a time- and dose-dependent manner. This uptake was via clathrin-dependent endocytosis. Furthermore, macrophage exosomes induced release of proinflammatory cytokines by the placenta. Taken together, our data demonstrates that exosomes are actively transported into the human placenta and that exosomes from activated immune cells modulate placental cytokine production. This represents a novel mechanism by which immune cells can signal to the placental unit, potentially facilitating responses to maternal inflammation and infection, and thereby preventing harm to the fetus.
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Beth
authors.initials: B
authors.lastname: Holder
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Tessa
authors.initials: T
authors.lastname: Jones
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.|Virology, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho Shimizu
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Rice
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Beverly
authors.initials: B
authors.lastname: Donaldson
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
authors.forename: Marielle
authors.initials: M
authors.lastname: Bouqueau
authors.affiliation: Division of Reproduction and Early Development, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), The University of Leeds, Leeds, UK.|Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Forbes
authors.affiliation: Section of Paediatrics, Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.|Vaccines & Immunity Theme, MRC Unit, Banjul, The Gambia.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D033261:Maternal-Fetal Relations / Q000523:psychology*; D010920:Placenta / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology
chemical_list: D016207:Cytokines
keywords: cytokines; endocytosis; exosomes; extracellular vesicles; immunology; macrophage; microvesicles; placenta; pregnancy; reproductive; trophoblast