#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Intravital Placenta Imaging Reveals Microcirculatory Dynamics Impact on Sequestration and Phagocytosis of -Infected Erythrocytes


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.


Vyšlo v časopise: Intravital Placenta Imaging Reveals Microcirculatory Dynamics Impact on Sequestration and Phagocytosis of -Infected Erythrocytes. PLoS Pathog 9(1): e32767. doi:10.1371/journal.ppat.1003154
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003154

Souhrn

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.


Zdroje

1. World Health Organization. A Strategic Framework for Malaria Prevention and Control During Pregnancy in the African Region. (2004).

2. DuffyPE, R.S. DesowitzRS (2001) Pregnancy malaria throughout history: dangerous labors. Malaria in Pregnancy. Deadly Parasite, Susceptible Host. Taylor and Francis 1–25.

3. AchurRN, ValiyaveettilM, AlkhalilA, OckenhouseCF, GowdaDC (2000) Characterization of proteoglycans of human placenta and identification of unique chondroitin sulfate proteoglycans of the intervillous spaces that mediate the adherence of Plasmodium falciparum-infected erythrocytes to the placenta. J Biol Chem 275: 40344–40356.

4. MuthusamyA, AchurRN, BhavanandanVP, FoudaGG, TaylorDW, et al. (2004) Plasmodium falciparum-infected erythrocytes adhere both in the intervillous space and on the villous surface of human placenta by binding to the low-sulfated chondroitin sulfate proteoglycan receptor. Am J Pathol 164: 2013–2025.

5. SalantiA, StaalsoeT, LavstsenT, JensenAT, SowaMP, et al. (2003) Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol 49: 179–191.

6. DuffyMF, MaierAG, ByrneTJ, MartyAJ, ElliottSR, et al. (2006) VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum. Mol Biochem Parasitol 148: 117–124.

7. SuguitanAL, LekeRG, FoudaG, ZhouA, ThuitaL, et al. (2003) Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. J Infect Dis 188: 1074–1082.

8. AbramsET, BrownH, ChensueSW, TurnerGD, TadesseE, et al. (2003) Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression. J Immunol 170: 2759–2764.

9. KhusmithS, DruilheP, GentiliniM (1982) Enhanced Plasmodium falciparum merozoite phagocytosis by monocytes from immune individuals. Infect Immun 35: 874–879.

10. WalterPR, GarinY, BlotP (1982) Placental pathologic changes in malaria. A histologic and ultrastructural study. Am J Pathol 109: 330–342.

11. BulmerJN, RasheedFN, MorrisonL, FrancisN, GreenwoodBM (1993) Placental malaria. II. A semi-quantitative investigation of the pathological features. Histopathology 22: 219–225.

12. LeopardiO, NaughtenW, SalviaL, ColecchiaM, MatteelliA, et al. (1996) Malaric placentas. A quantitative study and clinico-pathological correlations. Pathol Res Pract 192: 892–8.

13. FriedM, DuffyPE (1996) Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272: 1502–1504.

14. NeresR, MarinhoCR, GoncalvesLA, CatarinoMB, Penha-GoncalvesC (2008) Pregnancy outcome and placenta pathology in Plasmodium berghei ANKA infected mice reproduce the pathogenesis of severe malaria in pregnant women. PLoS One 3: e1608.

15. Rodrigues-DuarteL, Vieira de MoraesL, BarbozaR, MarinhoCR, Franke-FayardB, et al. (2012) Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57Bl/6 mouse. Malaria journal 11: 231.

16. CraigAG, GrauGE, JanseC, KazuraJW, MilnerD, et al. (2012) The Role of Animal Models for Research on Severe Malaria. PLoS Pathog 8: e1002401.

17. MalassineA, FrendoJL, Evain-BrionD (2003) A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update 9: 531–539.

18. WatsonED, CrossJC (2005) Development of structures and transport functions in the mouse placenta. Physiology (Bethesda) 20: 180–193.

19. MarinhoCR, NeresR, EpiphanioS, GoncalvesLA, CatarinoMB, et al. (2009) Recrudescent Plasmodium berghei from pregnant mice displays enhanced binding to the placenta and induces protection in multigravida. PLoS One 4: e5630.

20. CoanPM, Ferguson-SmithAC, BurtonGJ (2005) Ultrastructural changes in the interhaemal membrane and junctional zone of the murine chorioallantoic placenta across gestation. J Anat 207: 783–796.

21. PoovasseryJ, MooreJM (2009) Association of malaria-induced murine pregnancy failure with robust peripheral and placental cytokine responses. Infect Immun 77: 4998–5006.

22. PaviaCS, NiederbuhlCJ (1991) Immunization and protection against malaria during murine pregnancy. Am J Trop Med Hyg 44: 176–182.

23. ArbeilleP, CarlesG, BousquetF, BodyG, LansacJ (1998) Fetal cerebral and umbilical artery blood flow changes during pregnancy complicated by malaria. J Ultrasound Med 17: 223–229.

24. DormanEK, ShulmanCE, KingdomJ, BulmerJN, MwendwaJ, et al. (2002) Impaired uteroplacental blood flow in pregnancies complicated by falciparum malaria. Ultrasound Obstet Gynecol 19: 165–170.

25. IsmailMR, OrdiJ, MenendezC, VenturaPJ, AponteJJ, et al. (2000) Placental pathology in malaria: a histological, immunohistochemical, and quantitative study. Hum Pathol 31: 85–93.

26. ImamuraT, SugiyamaT, CuevasLE, MakundeR, NakamuraS (2002) Expression of tissue factor, the clotting initiator, on macrophages in Plasmodium falciparum-infected placentas. J Infect Dis 186: 436–440.

27. MuehlenbachsA, FriedM, McGreadyR, HarringtonWE, MutabingwaTK, et al. (2010) A novel histological grading scheme for placental malaria applied in areas of high and low malaria transmission. J Infect Dis 202: 1608–1616.

28. PoovasseryJS, SarrD, SmithG, NagyT, MooreJM (2009) Malaria-induced murine pregnancy failure: distinct roles for IFN-gamma and TNF. J Immunol 183: 5342–5349.

29. BrunelliR, MasselliG, ParasassiT, De SpiritoM, PapiM, et al. (2010) Intervillous circulation in intra-uterine growth restriction. Correlation to fetal well being. Placenta 31: 1051–1056.

30. LucchiNW, KoopmanR, PetersonDS, MooreJM (2006) Plasmodium falciparum-infected red blood cells selected for binding to cultured syncytiotrophoblast bind to chondroitin sulfate A and induce tyrosine phosphorylation in the syncytiotrophoblast. Placenta 27: 384–394.

31. LucchiNW, PetersonDS, MooreJM (2008) Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum. Malar J 7: 42.

32. LucchiNW, SarrD, OwinoSO, MwalimuSM, PetersonDS, et al. (2011) Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells. Placenta 32: 579–585.

33. ChaisavaneeyakornS, LucchiN, AbramowskyC, OthoroC, ChaiyarojSC, et al. (2005) Immunohistological characterization of macrophage migration inhibitory factor expression in Plasmodium falciparum-infected placentas. Infect Immun 73: 3287–3293.

34. ConroyA, SerghidesL, FinneyC, OwinoSO, KumarS, et al. (2009) C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria. PLoS ONE 4: e4953.

35. KabyemelaER, FriedM, KurtisJD, MutabingwaTK, DuffyPE (2008) Fetal responses during placental malaria modify the risk of low birth weight. Infect Immun 76: 1527–1534.

36. MuehlenbachsA, FriedM, LachowitzerJ, MutabingwaTK, DuffyPE (2008) Natural selection of FLT1 alleles and their association with malaria resistance in utero. Proc Natl Acad Sci USA 105: 14488–14491.

37. HviidL, MarinhoCR, StaalsoeT, Penha-GoncalvesC (2010) Of mice and women: rodent models of placental malaria. Trends Parasitol 26: 412–419.

38. JanseCJ, Franke-FayardB, MairGR, RamesarJ, ThielC, et al. (2006) High efficiency transfection of Plasmodium berghei facilitates novel selection procedures. Mol Biochem Parasitol 145: 60–70.

39. JanseCJ, Franke-FayardB, WatersAP (2006) Selection by flow-sorting of genetically transformed, GFP-expressing blood stages of the rodent malaria parasite, Plasmodium berghei. Nat Protoc 1: 614–623.

40. ZenclussenAC, OlivieriDN, DustinML, TadokoroCE (2012) In vivo multiphoton microscopy technique to reveal the physiology of the mouse placenta. Am J Reprod Immunol 68: 271–278.

41. FooksmanDR, SchwickertTA, VictoraGD, DustinML, NussenzweigMC, et al. (2010) Development and migration of plasma cells in the mouse lymph node. Immunity 33: 118–127.

42. FrenchAP, MillsS, SwarupR, BennettMJ, PridmoreTP (2008) Colocalization of fluorescent markers in confocal microscope images of plant cells. Nat Protoc 3: 619–628 Research Support, Non-U.S. Gov’t.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2013 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#