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    Plasmodium strain determines dendritic cell function essential for survival from malaria

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    Author
    Wykes, MN; Liu, XQ; Beattie, L; Stanisic, DI; Stacey, KJ; Smyth, MJ; Thomas, R; Good, MF
    Date
    2007-07-01
    Source Title
    PLoS Pathogens
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Beattie, Lynette
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Wykes, M. N., Liu, X. Q., Beattie, L., Stanisic, D. I., Stacey, K. J., Smyth, M. J., Thomas, R. & Good, M. F. (2007). Plasmodium strain determines dendritic cell function essential for survival from malaria. PLOS PATHOGENS, 3 (7), pp.904-912. https://doi.org/10.1371/journal.ppat.0030096.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253367
    DOI
    10.1371/journal.ppat.0030096
    Abstract
    The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs), we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes.

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