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Cutting Edge: Conventional Dendritic Cells Are the Critical APC Required for the Induction of Experimental Cerebral Malaria¹

Saskia deWalick^*,, Fiona H. Amante^*, Karli A. McSweeney^*, Louise M. Randall^*,, Amanda C. Stanley^*, Ashraful Haque^*, Rachel D. Kuns^*, Kelli P. A. MacDonald^*, Geoff R. Hill^* and Christian R. Engwerda^2,*

^* Queensland Institute of Medical Research, Herston, Australia; Leiden University Medical Centre, Leiden, The Netherlands; and School of Population Health, University of Queensland, Herston, Australia

Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection, causing significant morbidity and mortality among young children and nonimmune adults in the developing world. Although previous work on experimental CM has identified T cells as key mediators of pathology, the APCs and subsets therein required to initiate immunopathology remain unknown. In this study, we show that conventional dendritic cells but not plasmacytoid dendritic cells are required for the induction of malaria parasite-specific CD4⁺ T cell responses and subsequent experimental CM. These data have important implications for the development of malaria vaccines and the therapeutic management of CM.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Australian National Health and Medical Research Council.

² Address correspondence and reprint requests to Dr. Christian Engwerda, Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia. E-mail address: Christian.Engwerda{at}qimr.edu.au

³ Abbreviations used in this paper: CM, cerebral malaria; ECM, experimental CM; pRBC, parasitized RBC; nRBC, naive RBC: PbA, Plasmodium berghei ANKA; DC, dendritic cell; cDC, conventional DC; pDC, plasmacytoid DC; DTR, diphtheria toxin receptor; BM, bone marrow; p.i., postinfection; DT diphtheria toxin; CBA, cytometric bead array.

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