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Medical Microbiology and Immunology

, Volume 196, Issue 3, pp 127–133 | Cite as

Live and let die: manipulation of host hepatocytes by exoerythrocytic Plasmodium parasites

  • Angelika Sturm
  • Volker HeusslerEmail author
Review

Abstract

The generation of rodent Plasmodium strains expressing fluorescent proteins in all life cycle stages has had a big impact on malaria research. With this tool in hand, for the first time it was possible to follow in real time by in vivo microscopy the infection route of Plasmodium sporozoites transmitted to the mammalian host by Anopheles mosquitoes. Recently, this work has been extended to the analysis of both hepatocyte infection by Plasmodium sporozoites, as well as liver merozoite transport into blood vessels. The stunning results of these studies have considerably changed our understanding of hepatocyte invasion and parasite liberation. Here, we describe the most important findings of the last years and in addition, we elaborate on the molecular events during the intracellular development of Plasmodium exoerythrocytic forms that give rise to erythrocyte infecting merozoites.

Keywords

Exoerythrocytic Plasmodium parasites Merosome formation Intravital imaging Programmed cell death 

Notes

Acknowledgments

We thank Prof. M. Mota for providing the cartoon with the revised life cycle of Plasmodium. Gordon Langsley and Christina Deschermeier are thanked for critically reading the manuscript.

References

  1. 1.
    Laveran A (1881) De la nature parasitaire des accidents de l’impaludisme. CR Acad Sci Paris, pp 627–632Google Scholar
  2. 2.
    Sachs J, Malaney P (2002) The economic and social burden of malaria. Nature 415:680–685PubMedCrossRefGoogle Scholar
  3. 3.
    Amino R, Thiberge S, Martin B, Celli S, Shorte S, Frischknecht F, Menard R (2006) Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 12:220–224PubMedCrossRefGoogle Scholar
  4. 4.
    Frischknecht F, Baldacci P, Martin B, Zimmer C, Thiberge S, Olivo-Marin JC, Shorte SL, Menard R (2004) Imaging movement of malaria parasites during transmission by Anopheles mosquitoes. Cell Microbiol 6:687–694PubMedCrossRefGoogle Scholar
  5. 5.
    Mueller AK, Camargo N, Kaiser K, Andorfer C, Frevert U, Matuschewski K, Kappe SH (2005) Plasmodium liver stage developmental arrest by depletion of a protein at the parasite–host interface. Proc Natl Acad Sci U S A 102:3022–3027PubMedCrossRefGoogle Scholar
  6. 6.
    Mueller AK, Labaied M, Kappe SH, Matuschewski K (2005) Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature 433:164–167PubMedCrossRefGoogle Scholar
  7. 7.
    Nussenzweig RS, Vanderberg J, Most H, Orton C (1967) Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei. Nature 216:160–162PubMedCrossRefGoogle Scholar
  8. 8.
    Renia L, Gruner AC, Mauduit M, Snounou G (2006) Vaccination against malaria with live parasites. Expert Rev Vaccines 5:473–481PubMedCrossRefGoogle Scholar
  9. 9.
    Hill AV (2006) Pre-erythrocytic malaria vaccines: towards greater efficacy. Nat Rev Immunol 6:21–32PubMedCrossRefGoogle Scholar
  10. 10.
    Luke TC, Hoffman SL (2003) Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine. J Exp Biol 206:3803–3808PubMedCrossRefGoogle Scholar
  11. 11.
    Frevert U (2004) Sneaking in through the back entrance: the biology of malaria liver stages. Trends Parasitol 20:417–424PubMedCrossRefGoogle Scholar
  12. 12.
    Karnasuta C, Pavanand K, Chantakulkij S, Luttiwongsakorn N, Rassamesoraj M, Laohathai K, Webster HK, Watt G (1995) Complete development of the liver stage of Plasmodium falciparum in a human hepatoma cell line. Am J Trop Med Hyg 53:607–611PubMedGoogle Scholar
  13. 13.
    Mazier D, Beaudoin RL, Mellouk S, Druilhe P, Texier B, Trosper J, Miltgen F, Landau I, Paul C, Brandicourt O et al (1985) Complete development of hepatic stages of Plasmodium falciparum in vitro. Science 227:440–442PubMedCrossRefGoogle Scholar
  14. 14.
    Morosan S, Hez-Deroubaix S, Lunel F, Renia L, Giannini C, Van Rooijen N, Battaglia S, Blanc C, Eling W, Sauerwein R et al (2006) Liver-stage development of Plasmodium falciparum, in a humanized mouse model. J Infect Dis 193:996–1004PubMedCrossRefGoogle Scholar
  15. 15.
    Franke-Fayard B, Trueman H, Ramesar J, Mendoza J, van der Keur M, van der Linden R, Sinden RE, Waters AP, Janse CJ (2004) A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol 137:23–33PubMedCrossRefGoogle Scholar
  16. 16.
    Natarajan R, Thathy V, Mota MM, Hafalla JC, Menard R, Vernick KD (2001) Fluorescent Plasmodium berghei sporozoites and pre-erythrocytic stages: a new tool to study mosquito and mammalian host interactions with malaria parasites. Cell Microbiol 3:371–379PubMedCrossRefGoogle Scholar
  17. 17.
    Amino R, Thiberge S, Shorte S, Frischknecht F, Menard R (2006) Quantitative imaging of Plasmodium sporozoites in the mammalian host. C R Biol 329:858–862PubMedCrossRefGoogle Scholar
  18. 18.
    Frevert U, Engelmann S, Zougbede S, Stange J, Ng B, Matuschewski K, Liebes L, Yee H (2005) Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol 3:e192PubMedCrossRefGoogle Scholar
  19. 19.
    Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A, Krueger A, Pollok JM, Menard R, Heussler VT (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313:1287–1290PubMedCrossRefGoogle Scholar
  20. 20.
    Frevert U, Sinnis P, Cerami C, Shreffler W, Takacs B, Nussenzweig V (1993) Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes. J Exp Med 177:1287–1298PubMedCrossRefGoogle Scholar
  21. 21.
    Pradel G, Garapaty S, Frevert U (2002) Proteoglycans mediate malaria sporozoite targeting to the liver. Mol Microbiol 45:637–651PubMedCrossRefGoogle Scholar
  22. 22.
    Bergman LW, Kaiser K, Fujioka H, Coppens I, Daly TM, Fox S, Matuschewski K, Nussenzweig V, Kappe SH (2003) Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites. J Cell Sci 116:39–49PubMedCrossRefGoogle Scholar
  23. 23.
    Baer K, Roosevelt M, Clarkson AB Jr, van Rooijen N, Schnieder T, Frevert U (2007) Kupffer cells are obligatory for Plasmodium yoelii sporozoite infection of the liver. Cell Microbiol 9:397–412PubMedCrossRefGoogle Scholar
  24. 24.
    Mota MM, Pradel G, Vanderberg JP, Hafalla JC, Frevert U, Nussenzweig RS, Nussenzweig V, Rodriguez A (2001) Migration of Plasmodium sporozoites through cells before infection. Science 291:141–144PubMedCrossRefGoogle Scholar
  25. 25.
    Carrolo M, Giordano S, Cabrita-Santos L, Corso S, Vigario AM, Silva S, Leiriao P, Carapau D, Armas-Portela R, Comoglio PM et al (2003) Hepatocyte growth factor and its receptor are required for malaria infection. Nat Med 9:1363–1369PubMedCrossRefGoogle Scholar
  26. 26.
    van de Sand C, Horstmann S, Schmidt A, Sturm A, Bolte S, Krueger A, Lutgehetmann M, Pollok JM, Libert C, Heussler VT (2005) The liver stage of Plasmodium berghei inhibits host cell apoptosis. Mol Microbiol 58:731–742PubMedCrossRefGoogle Scholar
  27. 27.
    Doolan DL, Hoffman SL (2000) The complexity of protective immunity against liver-stage malaria. J Immunol 165:1453–1462PubMedGoogle Scholar
  28. 28.
    Meis JF, Verhave JP (1988) Exoerythrocytic development of malarial parasites. Adv Parasitol 27:1–61PubMedCrossRefGoogle Scholar
  29. 29.
    Hollingdale MR, Leland P, Schwartz AL (1983) In vitro cultivation of the exoerythrocytic stage of Plasmodium berghei in a hepatoma cell line. Am J Trop Med Hyg 32:682–684PubMedGoogle Scholar
  30. 30.
    Johnson DE (2000) Noncaspase proteases in apoptosis. Leukemia 14:1695–1703PubMedCrossRefGoogle Scholar
  31. 31.
    Stoka V, Turk B, Schendel SL, Kim TH, Cirman T, Snipas SJ, Ellerby LM, Bredesen D, Freeze H, Abrahamson M et al (2001) Lysosomal protease pathways to apoptosis. Cleavage of bid, not pro-caspases, is the most likely route. J Biol Chem 276:3149–3157PubMedCrossRefGoogle Scholar
  32. 32.
    Lockshin RA, Osborne B, Zakeri Z (2000) Cell death in the third millennium. Cell Death Differ 7:2–7PubMedCrossRefGoogle Scholar
  33. 33.
    Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688PubMedCrossRefGoogle Scholar
  34. 34.
    Rosenthal PJ (2004) Cysteine proteases of malaria parasites. Int J Parasitol 34:1489–1499PubMedCrossRefGoogle Scholar
  35. 35.
    Salmon BL, Oksman A, Goldberg DE (2001) Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc Natl Acad Sci USA 98:271–276PubMedCrossRefGoogle Scholar
  36. 36.
    Wickham ME, Culvenor JG, Cowman AF (2003) Selective inhibition of a two-step egress of malaria parasites from the host erythrocyte. J Biol Chem 278:37658–37663PubMedCrossRefGoogle Scholar
  37. 37.
    Delplace P, Bhatia A, Cagnard M, Camus D, Colombet G, Debrabant A, Dubremetz JF, Dubreuil N, Prensier G, Fortier B et al (1988) Protein p126: a parasitophorous vacuole antigen associated with the release of Plasmodium falciparum merozoites. Biol Cell 64:215–221PubMedCrossRefGoogle Scholar
  38. 38.
    Hodder AN, Drew DR, Epa VC, Delorenzi M, Bourgon R, Miller SK, Moritz RL, Frecklington DF, Simpson RJ, Speed TP et al (2003) Enzymic, phylogenetic, and structural characterization of the unusual papain-like protease domain of Plasmodium falciparum SERA5. J Biol Chem 278:48169–48177PubMedCrossRefGoogle Scholar
  39. 39.
    Li J, Matsuoka H, Mitamura T, Horii T (2002) Characterization of proteases involved in the processing of Plasmodium falciparum serine repeat antigen (SERA). Mol Biochem Parasitol 120:177–186PubMedCrossRefGoogle Scholar
  40. 40.
    Aoki S, Li J, Itagaki S, Okech BA, Egwang TG, Matsuoka H, Palacpac NM, Mitamura T, Horii T (2002) Serine repeat antigen (SERA5) is predominantly expressed among the SERA multigene family of Plasmodium falciparum, and the acquired antibody titers correlate with serum inhibition of the parasite growth. J Biol Chem 277:47533–47540PubMedCrossRefGoogle Scholar
  41. 41.
    Miller SK, Good RT, Drew DR, Delorenzi M, Sanders PR, Hodder AN, Speed TP, Cowman AF, de Koning-Ward TF, Crabb BS (2002) A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle. J Biol Chem 277:47524–47532PubMedCrossRefGoogle Scholar
  42. 42.
    Delplace P, Fortier B, Tronchin G, Dubremetz JF, Vernes A (1987) Localization, biosynthesis, processing and isolation of a major 126 kDa antigen of the parasitophorous vacuole of Plasmodium falciparum. Mol Biochem Parasitol 23:193–201PubMedCrossRefGoogle Scholar
  43. 43.
    Li J, Mitamura T, Fox BA, Bzik DJ, Horii T (2002) Differential localization of processed fragments of Plasmodium falciparum serine repeat antigen and further processing of its N-terminal 47 kDa fragment. Parasitol Int 51:343–352PubMedCrossRefGoogle Scholar
  44. 44.
    Aly AS, Matuschewski K (2005) A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocysts. J Exp Med 202:225–230PubMedCrossRefGoogle Scholar
  45. 45.
    Mempel TR, Scimone ML, Mora JR, von Andrian UH (2004) In vivo imaging of leukocyte trafficking in blood vessels and tissues. Curr Opin Immunol 16:406–417PubMedCrossRefGoogle Scholar
  46. 46.
    Millan J, Hewlett L, Glyn M, Toomre D, Clark P, Ridley AJ (2006) Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains. Nat Cell Biol 8:113–123PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Bernhard Nocht Institute for Tropical MedicineHamburgGermany

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