Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria

Author:

Pinzon-Charry Alberto12,Woodberry Tonia3,Kienzle Vivian1,McPhun Virginia14,Minigo Gabriela3,Lampah Daniel A.5,Kenangalem Enny5,Engwerda Christian1,López J. Alejandro12,Anstey Nicholas M.3,Good Michael F.14

Affiliation:

1. Queensland Institute of Medical Research, Brisbane QLD 4006, Australia

2. School of Biomolecular and Physical Sciences, Griffith University, Brisbane QLD 4111, Australia

3. Menzies School of Health Research, Charles Darwin University, Casuarina NT 0811, Australia

4. Institute for Glycomics, Griffith University, Gold Coast QLD 4222, Australia

5. District Health Authority and Menzies School of Health Research-National Institute of Health Research and Development Program, Timika, Papua 99962, Indonesia

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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