Browsing by Author "Megli, Christina"

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    Gatekeepers of the fetus: Characterization of placental macrophages.
    (The Journal of experimental medicine, 2021-01) Megli, Christina; Coyne, Carolyn B
    In this issue of JEM, Thomas et al. (https://doi.org/10.1084/jem.20200891) provide elegant technological and conceptual advances that further our understanding of the immune cells enriched at the maternal-fetal interface. Using new isolation strategies to better separate maternal- and fetal-derived cells, the authors identify previously undefined maternal-derived immune cells associated with the fetal-derived placenta and provide an in-depth analysis of the markers and characteristics of placental Hofbauer cells.
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    Inflammasome signaling in human placental trophoblasts regulates immune defense against Listeria monocytogenes infection.
    (The Journal of experimental medicine, 2021-01) Megli, Christina; Morosky, Stefanie; Rajasundaram, Dhivyaa; Coyne, Carolyn B
    The human placenta is a dynamic organ that modulates physiological adaptations to pregnancy. To define the immunological signature of the human placenta, we performed unbiased profiling of secreted immune factors from human chorionic villi isolated from placentas at mid and late stages of pregnancy. We show that placental trophoblasts constitutively secrete the inflammasome-associated cytokines IL-1β and IL-18, which is blocked by NLRP3 inflammasome inhibitors and occurs without detectable gasdermin D cleavage. We further show that placenta-derived IL-1β primes monocytes for inflammasome induction to protect against Listeria monocytogenes infection. Last, we show that the human placenta responds to L. monocytogenes infection through additional inflammasome activation and that inhibition of this pathway sensitizes villi to infection. Our results thus identify the inflammasome as an important mechanism by which the human placenta regulates systemic and local immunity during pregnancy to defend against L. monocytogenes infection.