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*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    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
    Pages (from-to)660-671
    Number of pages12
    JournalJournal of Infectious Diseases
    Volume219
    Issue number4
    DOIs
    Publication statusPublished - 29 Jan 2019

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