Scientific Reports (Jun 2017)

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

  • Jessica R. Loughland,
  • Gabriela Minigo,
  • Derek S. Sarovich,
  • Matt Field,
  • Peta E. Tipping,
  • Marcela Montes de Oca,
  • Kim A. Piera,
  • Fiona H. Amante,
  • Bridget E. Barber,
  • Matthew J. Grigg,
  • Timothy William,
  • Michael F. Good,
  • Denise L. Doolan,
  • Christian R. Engwerda,
  • Nicholas M. Anstey,
  • James S. McCarthy,
  • Tonia Woodberry

DOI
https://doi.org/10.1038/s41598-017-02096-2
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

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Abstract Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.