Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
      Pregnancy Complications, Parasitic*; Erythrocytes/*parasitology ; Microscopy, Fluorescence, Multiphoton/*methods ; Placenta/*pathology ; Plasmodium berghei/*physiology; Animals ; Blood Flow Velocity ; Erythrocytes/pathology ; Female ; Imaging, Three-Dimensional/methods ; Macrophages/metabolism ; Macrophages/parasitology ; Malaria/immunology ; Malaria/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microcirculation/physiology ; Phagocytosis/physiology ; Placenta/blood supply ; Placenta/parasitology ; Pregnancy ; Trophoblasts/metabolism ; Trophoblasts/parasitology
    • Abstract:
      Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE) sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The complex dynamics of placental microcirculation promotes IE accumulation in maternal blood spaces with low blood flow and allows the establishment of stable IE-trophoblast contacts. Further, we show that the fate of sequestered IE includes engulfment by both macrophagic and trophoblastic fetal-derived cells. These findings reinforce the current paradigm that IE interact with the trophoblast and provide definitive evidence on two novel pathogenesis mechanisms: (1) trophoblast layer controls placental microcirculation promoting IE sequestration; and (2) fetal-derived placental cells engulf sequestered IE.
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    • Publication Date:
      Date Created: 20130206 Date Completed: 20130808 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      PMC3561179
    • Accession Number:
      10.1371/journal.ppat.1003154
    • Accession Number:
      23382682