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Title: Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation.
Authors: Loughland, Jessica R
Minigo, Gabriela
Sarovich, Derek S
Field, Matt
Tipping, Peta E
Montes de Oca, Marcela
Piera, Kim A
Amante, Fiona H
Barber, Bridget E
Grigg, Matthew J
William, Timothy
Good, Michael F
Doolan, Denise L
Engwerda, Christian R
Anstey, Nicholas M
McCarthy, James S
Woodberry, Tonia
Citation: Scientific reports 2017-06-01; 7(1): 2596
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.
Click to open PubMed article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/28572564
Click to open Pubmed Article: https://www.ezpdhcs.nt.gov.au/login?url=https://www.ncbi.nlm.nih.gov/pubmed/28572564
Journal title: Scientific reports
Publication Date: 2017-06-01
Type: Journal Article
URI: https://hdl.handle.net/10137/5233
DOI: 10.1038/s41598-017-02096-2
Appears in Collections:(a) NT Health Research Collection

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