Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria

Jessica R. Loughland, Tonia Woodberry, Michelle J. Boyle, Peta E. Tipping, Kim A. Piera, Fiona H. Amante, Enny Kenangalem, Ric N. Price, Christian R. Engwerda, Nicholas M. Anstey, James S. McCarthy, Gabriela Minigo

Research output: Contribution to journalArticle

Abstract

Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs).

Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers.

Results: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function.

Conclusions: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.

Original languageEnglish
Article numberjiy555
Pages (from-to)660-671
Number of pages12
JournalThe Journal of infectious diseases
Volume219
Issue number4
Early online date15 Oct 2018
DOIs
Publication statusPublished - 29 Jan 2019

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    Loughland, J. R., Woodberry, T., Boyle, M. J., Tipping, P. E., Piera, K. A., Amante, F. H., Kenangalem, E., Price, R. N., Engwerda, C. R., Anstey, N. M., McCarthy, J. S., & Minigo, G. (2019). Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria. The Journal of infectious diseases, 219(4), 660-671. [jiy555]. https://doi.org/10.1093/infdis/jiy555