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

J Infect Dis. 2019 Jan 29;219(4):660-671. doi: 10.1093/infdis/jiy555.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Dendritic Cells / chemistry
  • Dendritic Cells / immunology*
  • Female
  • GPI-Linked Proteins / analysis
  • Humans
  • Interleukin-10 / metabolism*
  • Malaria, Falciparum
  • Male
  • Plasmodium falciparum / immunology*
  • Receptors, IgG / analysis
  • Tumor Necrosis Factor-alpha / metabolism*
  • Young Adult


  • FCGR3B protein, human
  • GPI-Linked Proteins
  • IL10 protein, human
  • Receptors, IgG
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10