Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria

Journal article

The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). Here, we show P. falciparum skewed CD16+ DC cytokine responses towards 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 following induced P. falciparum infection in malaria-naive volunteers. CD16+ DCs underwent distinctive activation, with increased expression of maturation markers HLA-DR and CD86, enhanced TNF production and co-production of TNF/IL-10. In vitro re-stimulation 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. 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.

Authors: Loughland, JR; Woodberry, T; Boyle, MJ; Tipping, PE; Piera, KA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Journal of Infectious Diseases
• Volume: 219
• Issue: 4
• Pages: 660–671
• Publication date: 2018-09-15
• Acceptance date: 2018-09-13
• DOI: 10.1093/infdis/jiy555
• EISSN: 1537-6613
• ISSN: 0022-1899
• Pmid: 30239833
• Language: English
• Keywords: CD16; IL-10; malaria; TNF; dendritic cells; human immune response; plasmodium falciparum