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Novel fibrillar structure confers adhesive property to malaria–infected erythrocytes

Abstract

Infections with the malaria parasite Plasmodium falciparum are characterized by sequestration of erythrocytes infected by mature forms of the parasite. Sequestration seems critical for the survival of the parasite, but may lead to excessive binding in the microvasculature and death of the human host. We report here that a novel electrondense fibrillar structure, containing immunoglobulins M or M and G, is found at the surface of infected erythrocytes that adhere to host cells. In cases of cerebral malaria, fibrillar strands are also seen in the microvasculature at autopsy. Our findings may explain the adhesive mechanism by which malaria–infected erythrocytes cause the vascular obstruction seen in complicated malaria infections.

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References

  1. Miller, L.H., Good, M.F. & Milon, G. Malaria pathogenesis. Science 264, 1878–1883 (1994).

    Article  CAS  Google Scholar 

  2. MacPherson, G.G., Warrell, M.J., White, N.J., Looareesuwan, S. & Warrell, D.A. Human cerebral malaria: A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am. J. Pathol. 119, 385–401 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Howard, R.J. & Gilladoga, A.D. Molecular studies related to the pathogenesis of cerebral malaria. Blood 74, 2603–2618 (1989).

    CAS  PubMed  Google Scholar 

  4. Trager, W., Rudzinska, M.A. & Bradbury, P.C. The fine structure of Plasmodium falciparum and its host erythrocyte in natural malarial infections in man. Bull. WHO 35, 883–885 (1966).

    CAS  PubMed  Google Scholar 

  5. Miller, L.H. The ultrastructure of red cells infected by Plasmodium falciparum in man. Trans. R. Soc. Trap. Med. Hyg. 66, 459–462 (1972).

    Article  CAS  Google Scholar 

  6. Ruangjirachuporn, W. et al. Cytoadherence of knobby and knobless Plasmodium falciparum-infected erythrocytes. Parasitology 102, 325–334 (1991).

    Article  Google Scholar 

  7. Carlson, J. et al. Human cerebral malaria: Association with erythrocyte resetting and lack of anti-rosetting antibodies. Lancet 336, 1457–1460 (1990).

    Article  CAS  Google Scholar 

  8. Treutiger, C.J. et al. Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria. Am. J. Trap. Med. Hyg. 46, 503–510 (1992).

    Article  CAS  Google Scholar 

  9. Ringwald, P. et al. Parasite virulence factors during falciparum malaria: Resetting, cytoadherance & modulation of cytoadherance by cytokines. Infect. Immun. 61, 5198–5204 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Rowe, A., Obeiro, J., Newbold, C.I. & Marsh, K. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect. Immun. 63, 2323–2326 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hidayat, A.A., Nalbandian, R.M., Sammons, D.W., Fleischman, J.A. & Johnson, T.E. The diagnostic histopathologic features of ocular malaria. Ophthalmology 100, 1183–1186 (1993).

    Article  CAS  Google Scholar 

  12. Riganti, M. et al. Human cerebral malaria in Thailand: A clinico-pathological correlation. Immunol. Let. 25, 199–206 (1990).

    Article  CAS  Google Scholar 

  13. Barnwell, J.W. et al. A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J. Clin. Invest. 84, 765–772 (1989).

    Article  CAS  Google Scholar 

  14. Berendt, A.R., Simmons, D.L., Tansey, J., Newbold, C.I. & Marsh, K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341, 57–59 (1989).

    Article  CAS  Google Scholar 

  15. Ockenhouse, C.F. et al. Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: Roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J. Exp. Med. 176, 1183–1189 (1992).

    Article  CAS  Google Scholar 

  16. Handunnetti, S.M. et al. Involvement of CD36 on erythrocytes as a resetting receptor for Plasmodium falciparum-infected erythrocytes. Blood 80, 2097–2104 (1992).

    CAS  PubMed  Google Scholar 

  17. Fujioka, H. et al. A nonhuman primate model for human cerebral malaria: Rhesus monkeys experimentally infected with Plasmodium fragile. Exp. Parasitol. 78, 371–376 (1994).

    Article  CAS  Google Scholar 

  18. Aikawa, M. Human cerebral malaria. Am. J. Trap. Med. Hyg. 39, 3–10 (1988).

    Article  CAS  Google Scholar 

  19. Nagatake, T. et al. Pathology of falciparum malaria in Vietnam. Am. J. Trap. Med. Hyg. 47, 259–264 (1992).

    Article  CAS  Google Scholar 

  20. Roberts, D.D. et al. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature 318, 64–66 (1985).

    Article  CAS  Google Scholar 

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Scholander, C., Treutiger, C., Hultenby, K. et al. Novel fibrillar structure confers adhesive property to malaria–infected erythrocytes. Nat Med 2, 204–208 (1996). https://doi.org/10.1038/nm0296-204

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