Apoptosis and Dysfunction of Blood Dendritic Cells in Patients with falciparum and vivax malaria

A PINZON-CHARRY, Tonia Woodberry, Vivian Kienzle, Virginia McPhun, Gabriela Minigo, Daniel Lampah, Enny Kenangalem, Christian Engwerda, Alejandro Lopez, Nicholas Anstey, Michael GOOD

    Research output: Contribution to journalArticle

    9 Downloads (Pure)

    Abstract

    Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC's immunotherapeutic potential. � 2013 Pinzon-Charry et al.
    Original languageEnglish
    Pages (from-to)1635-1646
    Number of pages12
    JournalJournal of Experimental Medicine
    Volume210
    Issue number8
    DOIs
    Publication statusPublished - 2013

    Fingerprint Dive into the research topics of 'Apoptosis and Dysfunction of Blood Dendritic Cells in Patients with falciparum and vivax malaria'. Together they form a unique fingerprint.

  • Cite this

    PINZON-CHARRY, A., Woodberry, T., Kienzle, V., McPhun, V., Minigo, G., Lampah, D., Kenangalem, E., Engwerda, C., Lopez, A., Anstey, N., & GOOD, M. (2013). Apoptosis and Dysfunction of Blood Dendritic Cells in Patients with falciparum and vivax malaria. Journal of Experimental Medicine, 210(8), 1635-1646. https://doi.org/10.1084/jem.20121972