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Plasmodium falciparum during pregnancy: a puzzling parasite tissue adhesion tropism

Published online by Cambridge University Press:  25 October 2007

M. C. NUNES  and
A. SCHERF
M. C. NUNES
Affiliation:
Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, CNRS, 75724 Paris, France
A. SCHERF*
Affiliation:
Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, CNRS, 75724 Paris, France
*
*Corresponding author: Artur Scherf, Unité de Biologie des Interactions Hôte-Parasite, CNRS URA 2581, Institut Pasteur, 25, rue du Dr. Roux, 75724 Paris Cedex 15, France. Tel: 33-1-45688616. Fax: 33-1-45688348. E-mail: ascherf@pasteur.fr
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Summary

P. falciparum malaria severely affects pregnant women and children. Despite immunity through lifelong exposure to malaria, pregnant women become susceptible to infections causing anaemia, abortions and low birth weight. They experience massive accumulation of infected erythrocytes (IEs) in the placenta. Adhesion of IEs to host endothelial receptors is mediated by members of a large diverse protein family called P. falciparum erythrocyte membrane protein 1 (PfEMP1). Pregnancy malaria is generally associated with the emergence of a distinct subset of parasites expressing a unique PfEMP1 that binds to the host-receptor chondroitin sulfate A (CSA). Resistance to pregnancy malaria is associated with the acquisition of antibodies that block IEs binding to placental CSA. The absence (or rare occurrence) of CSA-binding parasites in malaria patients (children, men and non-pregnant women) suggests that these parasites become virulent only during pregnancy. The molecular mechanisms used by P. falciparum to achieve the timely expression of the Pf-CSA ligand in pregnant women remain puzzling. In this review we will discuss two hypothetical mechanisms by which CSA-binding parasites may arise during pregnancy. The first, a selection process by the placenta of a distinct sub-population of P. falciparum expressing a particular PfEMP1. The second, an induction mechanism that facilitates the expression of a particular PfEMP1 protein by specific host factor(s) present only during pregnancy.

Keywords

MalariaplacentaPlasmodium falciparumvar2CSA
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 13: PARASITES IN PREGNANCY , December 2007 , pp. 1863 - 1869
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Achur, R. N., Valiyaveettil, M., Alkhalil, A., Ockenhouse, C. F. and Gowda, D. C. (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. Journal of Biological Chemistry 275, 40344–40356.Google Scholar
Achur, R. N., Valiyaveettil, M. and Gowda, D. C. (2003). The low sulfated chondroitin sulfate proteoglycans of human placenta have sulfate group-clustered domains that can efficiently bind Plasmodium falciparum-infected erythrocytes. Journal of Biological Chemistry 278, 11705–11713.Google Scholar
Alkhalil, A., Achur, R. N., Valiyaveettil, M., Ockenhouse, C. F. and Gowda, D. C. (2000). Structural requirements for the adherence of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate proteoglycans of human placenta. Journal of Biological Chemistry 275, 40357–40364.CrossRefGoogle ScholarPubMed
Avril, M., Traore, B., Costa, F. T., Lepolard, C. and Gysin, J. (2004). Placenta cryosections for study of the adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A in flow conditions. Microbes and Infection 6, 249–255.Google Scholar
Barnwell, J. W., Howard, R. J., Coon, H. G. and Miller, L. H. (1983). Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria. Infection and Immunity 40, 985–994.Google Scholar
Baruch, D. I., Pasloske, B. L., Singh, H. B., Bi, X., Ma, X. C., Feldman, M., Taraschi, T. F. and Howard, R. J. (1995). Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82, 77–87.Google Scholar
Beeson, J. G., Brown, G. V., Molyneux, M. E., Mhango, C., Dzinjalamala, F. and Rogerson, S. J. (1999). Plasmodium falciparum isolates from infected pregnant women and children are associated with distinct adhesive and antigenic properties. Journal of Infectious Diseases 180, 464–472.Google Scholar
Beeson, J. G., Rogerson, S. J., Cooke, B. M., Reeder, J. C., Chai, W., Lawson, A. M., Molyneux, M. E. and Brown, G. V. (2000). Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nature Medicine 6, 86–90.Google Scholar
Benten, W. P., Wunderlich, F. and Mossmann, H. (1992 a). Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity. Experimental Parasitology 75, 240–247.Google Scholar
Benten, W. P., Wunderlich, F. and Mossmann, H. (1992 b). Testosterone-induced suppression of self-healing Plasmodium chabaudi malaria: an effect not mediated by androgen receptors? Journal of Endocrinology 135, 407–413.Google Scholar
Bouyou-Akotet, M. K., Adegnika, A. A., Agnandji, S. T., Ngou-Milama, E., Kombila, M., Kremsner, P. G. and Mavoungou, E. (2005). Cortisol and susceptibility to malaria during pregnancy. Microbes and Infection 7, 1217–1223.Google Scholar
Bouyou-Akotet, M. K., Issifou, S., Meye, J. F., Kombila, M., Ngou-Milama, E., Luty, A. J., Kremsner, P. G. and Mavoungou, E. (2004). Depressed natural killer cell cytotoxicity against Plasmodium falciparum-infected erythrocytes during first pregnancies. Clinical Infectious Diseases 38, 342–347.Google Scholar
Bowen, J. M., Chamley, L., Keelan, J. A. and Mitchell, M. D. (2002). Cytokines of the placenta and extra-placental membranes: roles and regulation during human pregnancy and parturition. Placenta 23, 257–273.Google Scholar
Brown, K. N. (1973). Antibody induced variation in malaria parasites. Nature 242, 49–50.Google Scholar
Craig, A. and Scherf, A. (2001). Molecules on the surface of the Plasmodium falciparum-infected erythrocyte and their role in malaria pathogenesis and immune evasion. Molecular and Biochemical Parasitology 115, 129–143.Google Scholar
Creasey, A. M., Staalsoe, T., Raza, A., Arnot, D. E. and Rowe, J. A. (2003). Nonspecific immunoglobulin M binding and chondroitin sulfate A binding are linked phenotypes of Plasmodium falciparum isolates implicated in malaria during pregnancy. Infection and Immunity 71, 4767–4771.Google Scholar
David, P. H., Hommel, M., Miller, L. H., Udeinya, I. J. and Oligino, L. D. (1983). Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proceedings of the National Academy of Sciences, USA 80, 5075–5079.Google Scholar
Dittman, W. A. and Majerus, P. W. (1990). Structure and function of thrombomodulin: a natural anticoagulant. Blood 75, 329–336.Google Scholar
Duffy, P. E. and Fried, M. (2003). Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A are associated with increased birth weight and the gestational age of newborns. Infection and Immunity 71, 6620–6623.CrossRefGoogle ScholarPubMed
Duraisingh, M. T., Voss, T. S., Marty, A. J., Duffy, M. F., Good, R. T., Thompson, J. K., Freitas-Junior, L. H., Scherf, A., Crabb, B. S. and Cowman, A. F. (2005). Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 121, 13–24.Google Scholar
Flick, K., Scholander, C., Chen, Q., Fernandez, V., Pouvelle, B., Gysin, J. and Wahlgren, M. (2001). Role of nonimmune IgG bound to PfEMP1 in placental malaria. Science 293, 2098–2100.Google Scholar
Freitas-Junior, L. H., Hernandez-Rivas, R., Ralph, S. A., Montiel-Condado, D., Ruvalcaba-Salazar, O. K., Rojas-Meza, A. P., Mancio-Silva, L., Leal-Silvestre, R. J., Gontijo, A. M., Shorte, S. et al. (2005). Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 121, 25–36.Google Scholar
Fried, M., Domingo, G. J., Gowda, C. D., Mutabingwa, T. K. and Duffy, P. E. (2006). Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion of parasitized erythrocytes in the placenta. Experimental Parasitology 113, 36–42.CrossRefGoogle ScholarPubMed
Fried, M. and Duffy, P. E. (1996). Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272, 1502–1504.CrossRefGoogle ScholarPubMed
Fried, M., Muga, R. O., Misore, A. O. and Duffy, P. E. (1998 a). Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. Journal of Immunology 160, 2523–2530.Google Scholar
Fried, M., Nosten, F., Brockman, A., Brabin, B. J. and Duffy, P. E. (1998 b). Maternal antibodies block malaria. Nature 395, 851–852.Google Scholar
Galinski, M. R. and Corredor, V. (2004). Variant antigen expression in malaria infections: posttranscriptional gene silencing, virulence and severe pathology. Molecular and Biochemical Parasitology 134, 17–25.Google Scholar
Gamain, B., Trimnell, A. R., Scheidig, C., Scherf, A., Miller, L. H. and Smith, J. D. (2005). Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites. Journal of Infectious Diseases 191, 1010–1013.CrossRefGoogle ScholarPubMed
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S. et al. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511.Google Scholar
Horrocks, P., Pinches, R., Christodoulou, Z., Kyes, S. A. and Newbold, C. I. (2004). Variable var transition rates underlie antigenic variation in malaria. Proceedings of the National Academy of Sciences, USA 101, 11129–11134.Google Scholar
Hotta, C. T., Gazarini, M. L., Beraldo, F. H., Varotti, F. P., Lopes, C., Markus, R. P., Pozzan, T. and Garcia, C. R. (2000). Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites. Nature Cell Biology 2, 466–468.Google Scholar
Kyes, S., Horrocks, P. and Newbold, C. (2001). Antigenic variation at the infected red cell surface in malaria. Annual Review of Microbiology 55, 673–707.Google Scholar
Lavstsen, T., Salanti, A., Jensen, A. T., Arnot, D. E. and Theander, T. G. (2003). Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. Malaria Journal 2, 27.Google Scholar
Luft, B. J. and Remington, J. S. (1982). Effect of pregnancy on resistance to Listeria monocytogenes and Toxoplasma gondii infections in mice. Infection and Immunity 38, 1164–1171.Google Scholar
Lyden, T. W., Robinson, J. M., Tridandapani, S., Teillaud, J. L., Garber, S. A., Osborne, J. M., Frey, J., Budde, P. and Anderson, C. L. (2001). The Fc receptor for IgG expressed in the villus endothelium of human placenta is Fc gamma RIIb2. Journal of Immunology 166, 3882–3889.Google Scholar
Menendez, C. (1995). Malaria during pregnancy: a priority area of malaria research and control. Parasitology Today 11, 178–183.Google Scholar
Miller, L. H., Baruch, D. I., Marsh, K. and Doumbo, O. K. (2002). The pathogenic basis of malaria. Nature 415, 673–679.Google Scholar
Miller, L. H., Good, M. F. and Milon, G. (1994). Malaria pathogenesis. Science 264, 1878–1883.Google Scholar
Muthusamy, A., Achur, R. N., Bhavanandan, V. P., Fouda, G. G., Taylor, D. W. and Gowda, D. C. (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. American Journal of Pathology 164, 2013–2025.Google Scholar
Pasloske, B. L. and Howard, R. J. (1994). Malaria, the red cell, and the endothelium. Annual Review of Medicine 45, 283–295.Google Scholar
Peters, J., Fowler, E., Gatton, M., Chen, N., Saul, A. and Cheng, Q. (2002). High diversity and rapid changeover of expressed var genes during the acute phase of Plasmodium falciparum infections in human volunteers. Proceedings of the National Academy of Sciences, USA 99, 10689–10694.Google Scholar
Pouvelle, B., Meyer, P., Robert, C., Bardel, L. and Gysin, J. (1997). Chondroitin-4-sulfate impairs in vitro and in vivo cytoadherence of Plasmodium falciparum-infected erythrocytes. Molecular Medicine 3, 508–518.Google Scholar
Pouvelle, B., Traore, B., Nogueira, P. A., Pradines, B., LePolard, C. and Gysin, J. (2003). Modeling of Plasmodium falciparum-infected erythrocyte cytoadhesion in microvascular conditions: chondroitin-4-sulfate binding, A competitive phenotype. Journal of Infectious Diseases 187, 292–302.Google Scholar
Ralph, S. A. and Scherf, A. (2005). The epigenetic control of antigenic variation in Plasmodium falciparum. Current Opinion in Microbiology 8, 434–440.CrossRefGoogle ScholarPubMed
Rasti, N., Namusoke, F., Chene, A., Chen, Q., Staalsoe, T., Klinkert, M. Q., Mirembe, F., Kironde, F. and Wahlgren, M. (2006). Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin. Proceedings of the National Academy of Sciences, USA 103, 13795–13800.Google Scholar
Ricke, C. H., Staalsoe, T., Koram, K., Akanmori, B. D., Riley, E. M., Theander, T. G. and Hviid, L. (2000). Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A. Journal of Immunology 165, 3309–3316.Google Scholar
Robert, C., Pouvelle, B., Meyer, P., Muanza, K., Fujioka, H., Aikawa, M., Scherf, A. and Gysin, J. (1995). Chondroitin-4-sulphate (proteoglycan), a receptor for Plasmodium falciparum-infected erythrocyte adherence on brain microvascular endothelial cells. Research in Immunology 146, 383–393.Google Scholar
Roberts, C. W., Satoskar, A. and Alexander, J. (1996). Sex steroids, pregnancy-associated hormones and immunity to parasitic infection. Parasitology Today 12, 382–388.Google Scholar
Roberts, C. W., Walker, W. and Alexander, J. (2001). Sex-associated hormones and immunity to protozoan parasites. Clinical Microbiology Reviews 14, 476–488.Google Scholar
Roberts, D. J., Craig, A. G., Berendt, A. R., Pinches, R., Nash, G., Marsh, K. and Newbold, C. I. (1992). Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357, 689–692.Google Scholar
Rogerson, S. J. and Brown, G. V. (1997). Chondroitin sulphate A as an adherence receptor for Plasmodium falciparum-infected erythrocytes. Parasitology Today 13, 70–75.CrossRefGoogle ScholarPubMed
Salanti, A., Dahlback, M., Turner, L., Nielsen, M. A., Barfod, L., Magistrado, P., Jensen, A. T., Lavstsen, T., Ofori, M. F., Marsh, K. et al. (2004). Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. Journal of Experimental Medicine 200, 1197–1203.CrossRefGoogle ScholarPubMed
Salanti, A., Staalsoe, T., Lavstsen, T., Jensen, A. T., Sowa, M. P., Arnot, D. E., Hviid, L. and Theander, T. G. (2003). Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Molecular Microbiology 49, 179–191.Google Scholar
Scherf, A., Hernandez-Rivas, R., Buffet, P., Bottius, E., Benatar, C., Pouvelle, B., Gysin, J. and Lanzer, M. (1998). Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO Journal 17, 5418–5426.Google Scholar
Shirahata, T., Muroya, N., Ohta, C., Goto, H. and Nakane, A. (1992). Correlation between increased susceptibility to primary Toxoplasma gondii infection and depressed production of gamma interferon in pregnant mice. Microbiology and Immunology 36, 81–91.Google Scholar
Silamut, K., Phu, N. H., Whitty, C., Turner, G. D., Louwrier, K., Mai, N. T., Simpson, J. A., Hien, T. T. and White, N. J. (1999). A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. American Journal of Pathology 155, 395–410.Google Scholar
Smith, J. D., Chitnis, C. E., Craig, A. G., Roberts, D. J., Hudson-Taylor, D. E., Peterson, D. S., Pinches, R., Newbold, C. I. and Miller, L. H. (1995). Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82, 101–110.Google Scholar
Su, X. Z., Heatwole, V. M., Wertheimer, S. P., Guinet, F., Herrfeldt, J. A., Peterson, D. S., Ravetch, J. A. and Wellems, T. E. (1995). The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89–100.Google Scholar
Traore, B., Muanza, K., Looareesuwan, S., Supavej, S., Khusmith, S., Danis, M., Viriyavejakul, P. and Gay, F. (2000). Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model. American Journal of Tropical Medicine and Hygiene 62, 38–44.Google Scholar
Tuikue Ndam, N. G., Fievet, N., Bertin, G., Cottrell, G., Gaye, A. and Deloron, P. (2004). Variable adhesion abilities and overlapping antigenic properties in placental Plasmodium falciparum isolates. Journal of Infectious Diseases 190, 2001–2009.Google Scholar
Valiyaveettil, M., Achur, R. N., Alkhalil, A., Ockenhouse, C. F. and Gowda, D. C. (2001). Plasmodium falciparum cytoadherence to human placenta: evaluation of hyaluronic acid and chondroitin 4-sulfate for binding of infected erythrocytes. Experimental Parasitology 99, 57–65.Google Scholar
Viebig, N. K., Gamain, B., Scheidig, C., Lepolard, C., Przyborski, J., Lanzer, M., Gysin, J. and Scherf, A. (2005). A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A. EMBO Reports 6, 775–781.Google Scholar
Vleugels, M. P., Brabin, B., Eling, W. M. and de Graaf, R. (1989). Cortisol and Plasmodium falciparum infection in pregnant women in Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 173–177.Google Scholar
Warrell, D. A. (1987). Pathophysiology of severe falciparum malaria in man. Parasitology 94 (Suppl.) S53–S76.CrossRefGoogle ScholarPubMed
Wegmann, T. G., Lin, H., Guilbert, L. and Mosmann, T. R. (1993). Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunology Today 14, 353–356.Google Scholar
Wong, V. L., Hofman, F. M., Ishii, H. and Fisher, M. (1991). Regional distribution of thrombomodulin in human brain. Brain Research 556, 1–5.Google Scholar