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

Prinzon-Charry, Alberto, Woodberry, Tonia, Kienzle, Vivian, McPhun, Virginia, Minigo, Gabriela, Lampah, Daniel, Kenangalem, Enny, Engwerda, Christian, Lopez, Alejandro, Anstey, Nicholas M. and Good, Michael F. (2013). Apoptosis and Dysfunction of Blood Dendritic Cells in Patients with falciparum and vivax malaria. Journal of Experimental Medicine,210(8):1635-1646.

Document type: Journal Article
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IRMA ID bsmithxPUB183
Title Apoptosis and Dysfunction of Blood Dendritic Cells in Patients with falciparum and vivax malaria
Author Prinzon-Charry, Alberto
Woodberry, Tonia
Kienzle, Vivian
McPhun, Virginia
Minigo, Gabriela
Lampah, Daniel
Kenangalem, Enny
Engwerda, Christian
Lopez, Alejandro
Anstey, Nicholas M.
Good, Michael F.
Journal Name Journal of Experimental Medicine
Publication Date 2013
Volume Number 210
Issue Number 8
ISSN 0022-1007   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84884214616
Start Page 1635
End Page 1646
Total Pages 12
Place of Publication United States of America
Publisher Rockefeller University Press
HERDC Category C1 - Journal Article (DIISR)
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.

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Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 3.0 License

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