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Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells

Nature volume 400, pages 73–77 (1999)Cite this article

Abstract

The malaria parasite Plasmodium falciparum is one of the most successful human pathogens. Specific virulence factors remain poorly defined, although the adhesion of infected erythrocytes tothe venular endothelium has been associated with some of thesyndromes of severe disease1. Immune responses cannot prevent the development of symptomatic infections throughout life, and clinical immunity to the disease develops only slowly during childhood. An understanding of the obstacles to the development of protective immunity is crucial for developing rational approaches to prevent the disease. Here we show that intact malaria-infected erythrocytes adhere to dendritic cells, inhibit the maturation of dendritic cells and subsequently reduce their capacity to stimulate T cells. These data demonstrate both a novel mechanism by which malaria parasites induce immune dysregulation and a functional role beyond endothelial adhesion for the adhesive phenotypes expressed at the surface of infected erythrocytes.

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Figure 1: Expression of surface markers on dendritic cells in response to LPS.
Figure 2: Only cytoadherent parasite lines inhibit dendritic-cell maturation.
Figure 3: Transmission electron micrographs illustrating the interaction of dendritic cells with infected erythrocytes.
Figure 4: Dendritic cells (DC) exposed to intact infected erythrocytes are poor stimulators of primary T-cell responses.
Figure 5: Dendritic cells exposed to intact infected erythrocytes are poor stimulators of secondary T-cell responses.

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Acknowledgements

We thank T. F. Tedder for the gift of anti-CD83 monoclonal antibody, D. Chao, P.Bahl, L. Corlett and K. Pulford for technical advice and C. Newbold, A. Vincent, B. C. Elford and S.Roberts for support and encouragement. D.J.P.F. was supported by the Wellcome Trust. D.J.R. is a Wellcome Trust Senior Fellow in Clinical Science and B.C.U. was supported by a Fellowship from the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Institute of Molecular Medicine, Headington, OX3 9DU, Oxford, UK

    Britta C. Urban, Arnab Pain, Nick Willcox & David J. Roberts

  2. Nuffield Department of Pathology, Headington, OX3 9DU, Oxford, UK

    David J. P. Ferguson

  3. Molecular Immunology Group, Headington, OX3 9DU, Oxford, UK

    Magdalena Plebanski

  4. Nuffield Department of Surgery, Headington, OX3 9DU, Oxford, UK

    Jonathan M. Austyn

  5. National Blood ServiceOxford Centre, John Radcliffe Hospital, Headington, OX3 9DU, Oxford, UK

    David J. Roberts

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  1. Britta C. Urban
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Correspondence to David J. Roberts.

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Urban, B., Ferguson, D., Pain, A. et al. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400, 73–77 (1999). https://doi.org/10.1038/21900

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