title: Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes.
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.
authors: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors: Luciana Vieira
authors: LV
authors: de Moraes
authors: Carlos Eduardo
authors: CE
authors: Tadokoro
authors: Iván
authors: I
authors: Gómez-Conde
authors: David N
authors: DN
authors: Olivieri
authors: Carlos
authors: C
authors: Penha-Gonçalves
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D010587:Phagocytosis / Q000502:physiology; D010920:Placenta / Q000098:blood supply / Q000469:parasitology / Q000473:pathology*; D010962:Plasmodium berghei / Q000502:physiology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D014327:Trophoblasts / Q000378:metabolism / Q000469:parasitology
references: Nat Protoc. 2006;1(2):614-23
references: 17406288
references: Immunity. 2010 Jul 23;33(1):118-27
references: 20619695
references: Placenta. 2011 Aug;32(8):579-85
references: 21632106
references: J Immunol. 2003 Mar 1;170(5):2759-64
references: 12594307
references: Science. 1996 Jun 7;272(5267):1502-4
references: 8633247
references: Malar J. 2012 Jul 16;11:231
references: 22799533
references: Placenta. 2006 Apr-May;27(4-5):384-94
references: 16009422
references: Placenta. 2010 Dec;31(12):1051-6
references: 20970852
references: J Immunol. 2009 Oct 15;183(8):5342-9
references: 19783682
references: J Infect Dis. 2003 Oct 1;188(7):1074-82
references: 14513430
references: Infect Immun. 2008 Apr;76(4):1527-34
references: 18212078
references: Pathol Res Pract. 1996 Sep;192(9):892-8; discussion 899-900
references: 8950755
references: Histopathology. 1993 Mar;22(3):219-25
references: 8495955
references: Hum Pathol. 2000 Jan;31(1):85-93
references: 10665918
references: Am J Pathol. 1982 Dec;109(3):330-42
references: 6758604
references: PLoS One. 2009 May 20;4(5):e5630
references: 19461965
references: Mol Biochem Parasitol. 2006 Aug;148(2):117-24
references: 16631964
references: Infect Immun. 1982 Mar;35(3):874-9
references: 7040248
references: Am J Trop Med Hyg. 1991 Feb;44(2):176-82
references: 2012261
references: J Anat. 2005 Dec;207(6):783-96
references: 16367805
references: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14488-91
references: 18779584
references: PLoS One. 2009;4(3):e4953
references: 19308263
references: Hum Reprod Update. 2003 Nov-Dec;9(6):531-9
references: 14714590
references: J Infect Dis. 2002 Aug 1;186(3):436-40
references: 12134244
references: Infect Immun. 2005 Jun;73(6):3287-93
references: 15908353
references: Trends Parasitol. 2010 Aug;26(8):412-9
references: 20605743
references: Mol Microbiol. 2003 Jul;49(1):179-91
references: 12823820
references: J Biol Chem. 2000 Dec 22;275(51):40344-56
references: 11005814
references: PLoS Pathog. 2012 Feb;8(2):e1002401
references: 22319438
references: Malar J. 2008 Feb 29;7:42
references: 18312657
references: Physiology (Bethesda). 2005 Jun;20:180-93
references: 15888575
references: Nat Protoc. 2008;3(4):619-28
references: 18388944
references: Infect Immun. 2009 Nov;77(11):4998-5006
references: 19687196
references: J Infect Dis. 2010 Nov 15;202(10):1608-16
references: 20929353
references: PLoS One. 2008 Feb 13;3(2):e1608
references: 18270595
references: J Ultrasound Med. 1998 Apr;17(4):223-9
references: 9544605
references: Mol Biochem Parasitol. 2006 Jan;145(1):60-70
references: 16242190
references: Am J Reprod Immunol. 2012 Sep;68(3):271-8
references: 22626451
references: Am J Pathol. 2004 Jun;164(6):2013-25
references: 15161637
references: Ultrasound Obstet Gynecol. 2002 Feb;19(2):165-70
references: 11876809